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Arroyave, Jose, Juan Manuel Carretero y Domenico Gruosso. "Isolated aortic dilation without osteoarthritis: a case of SMAD3 mutation". Cardiology in the Young 28, n.º 5 (15 de febrero de 2018): 765–67. http://dx.doi.org/10.1017/s1047951118000082.
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AbstractAneurysm–osteoarthritis syndrome is a recently discovered inherited autosomal dominant connective tissue disease caused by SMAD3 mutations. Aneurysm–osteoarthritis syndrome is responsible for 2% of familial thoracic aortic aneurysms and dissections and is characterised by aneurysms, dissections, and tortuosity throughout the arterial tree in combination with osteoarthritis. Early-onset osteoarthritis is present in almost all patients. We present the case of a non-syndromic young boy with SMAD3 mutation isolated from the dilated aortic root and ascending aorta without osteoarthritis.
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Patuzzo, Cristina, A. Pasquali, E. Trabetti, G. Malerba, PF Pignatii, M. Tessari y G. Faggian. "A Preliminary microRNA Analysis of non Syndromic Thoracic Aortic Aneurysms". Balkan Journal of Medical Genetics 15, Supplement (1 de diciembre de 2012): 51–55. http://dx.doi.org/10.2478/v10034-012-0019-6.
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ABSTRACT The development of thoracic aortic aneurysms (TAAs) involves a multifactorial process resulting in alterations of the structure and composition of the extracellular matrix (ECM). Recently, modifications in microRNA (miRNA) expression were implicated in the pathogenesis of TAA. This study presents a preliminary miRNA microarray analysis conducted on pooled ascending aorta RNAs obtained from non familial non syndromic TAA patients (five males and five females) compared to matched control pools. Ninety-nine differentially expressed miRNAs with >1.5-foldup- or down-regulation in TAAs compared to controls were identified, 16.0% of which were similarly regulated in the two sexes. Genes putatively targeted by differentially expressed miRNAs belonged preferentially to focal adhesion and adherens junction pathways. The results indicate an altered regulation of miRNA-mediated gene expression in the cellular interactions of aneurysmal aortic wall.
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Fitzgerald, Kristi K., Abdul Majeed Bhat, Katrina Conard, James Hyland y Christian Pizarro. "NovelSMAD3Mutation in a Patient with Hypoplastic Left Heart Syndrome with Significant Aortic Aneurysm". Case Reports in Genetics 2014 (2014): 1–4. http://dx.doi.org/10.1155/2014/591516.
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Aneurysms-osteoarthritis syndrome (AOS) caused by haploinsufficiency ofSMAD3is a recently described cause of syndromic familial thoracic aortic aneurysm and dissection (TAAD). We identified a novelSMAD3mutation in a patient with hypoplastic left heart syndrome (HLHS) who developed progressive aortic aneurysm requiring surgical replacement of the neoaortic root, ascending aorta, and proximal aortic arch. Family screening for the mutation revealed that his father, who has vascular and skeletal features of AOS, and his brother, who is asymptomatic, also have the pathogenic mutation. This is the first case report of aSMAD3mutation in a patient with hypoplastic left heart syndrome. This case highlights the importance of genetic testing for known causes of aneurysm in patients with congenital heart disease who develop aneurysmal disease as it may significantly impact the management of those patients and their family members.
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Panfilov, D. S., V. V. Saushkin, E. L. Sonduev, S. I. Sazonova y B. N. Kozlov. "Gender-specifi c differences in ascending aortic surgery". Siberian Journal of Clinical and Experimental Medicine 37, n.º 3 (20 de octubre de 2022): 108–13. http://dx.doi.org/10.29001/2073-8552-2022-37-3-108-113.
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Introduction. According to recent data, thoracic aortic surgery have reduced morbidity and mortality, however, women are at increased postoperative risk of adverse outcomes. Our aim was to evaluate and compare early outcomes in male and female patients undergoing ascending aortic replacement.Methods. A total of 88 patients, consisting of 54 men (61.4%) and 34 women (38.6%) underwent ascending aortic surgery for non-syndromic aneurysms from January 2013 to December 2021. We analyzed clinical outcomes between males and females.Results. According to computed tomographic angiography, preoperative normalized aortic diameters were significantly larger in females (2.9 [2.7; 3.2] cm/m2) vs. (2.5 [2.3; 2.6] cm/m2, p < 0.001) in males, without differences in absolute values (51 [49; 53] mm vs. 52 [50; 53] mm, p = 0.356). There were no significant differences in neurological, cardiac, pulmonary, and renal complications in both groups in the early postoperative period. In-hospital mortality was 1.9% and 5.9% (p = 0.307) in male and female patients, respectively.Conclusions. Ascending aortic surgery for aneurysms below 5.5 cm threshold has tolerable early outcomes both in men and women.
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Federspiel, Jan M., Philipp A. Schnabel, Thomas Tschernig, Brittany Balint, Tanja Schwab, Matthias W. Laschke y Hans-Joachim Schäfers. "Aortic aneurysms with tricuspid aortic valve have more degeneration than unicuspid aortic valve aneurysms". European Journal of Cardio-Thoracic Surgery 60, n.º 2 (1 de marzo de 2021): 333–40. http://dx.doi.org/10.1093/ejcts/ezab101.
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Abstract OBJECTIVES The unicuspid aortic valve (UAV) is a rare cardiac malformation and is associated with the formation of ascending aortic aneurysms. To characterize its associated aortic wall changes, normal and aneurysmatic ascending aortic wall specimens were analysed, focusing on the potential mechanisms of aneurysm formation. Patients with tricuspid aortic valve (TAV) served as controls. METHODS In a retrospective observational study, 74 specimens (dilated and non-dilated aortas; individuals with UAV and TAV) obtained intraoperatively were studied. Standard stains and immunohistochemical labelling of cleaved caspase-3, cluster of differentiation 31 and endothelial nitric oxide synthase (eNOS) were performed to assess the degree of apoptosis, distribution of eNOS within the aortic wall, smooth muscle cell (SMC) nuclei loss and mucoid extracellular matrix accumulation (MEMA). RESULTS Deeper ingrowth of vasa vasorum was found in dilated aortas. Interestingly, eNOS was expressed mostly in vasa vasorum. More apoptosis was seen in UAV aortas compared to TAV aortas (P < 0.001). Both UAV and TAV aortas were comparable regarding SMC nuclei loss (P = 0.419). In dilated compared to non-dilated aortas regardless valve morphology SMC nuclei loss was increased (P = 0.005) and more pronounced translamellar MEMA was present (P = 0.011). The highest grade of distribution (P = 0.043) and the highest severity (P = 0.005) regarding MEMA were seen in TAV dilated specimens compared to UAV dilated specimens. CONCLUSIONS Aneurysms with UAV show increased apoptosis, the role of which is unclear. Strikingly, more severe MEMA was found in TAV aneurysms compared to UAV aneurysms. Thus, UAV-associated aortic wall changes and resulting aneurysm may be less aggressive than aneurysms with TAV.
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Chen, Zheying, Alan Daugherty y Mary Sheppard. "2464 Sexual dimorphism in a mouse model of syndromic thoracic aortic aneurysm". Journal of Clinical and Translational Science 2, S1 (junio de 2018): 27. http://dx.doi.org/10.1017/cts.2018.121.
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OBJECTIVES/SPECIFIC AIMS: Pre-clinical and clinical observations have noted that increased aortic dilation is associated with male sex. Using an experimental model of severe, syndromic thoracic aortic aneurysms, we quantify aortic dilation and elastin stability in male Versus female mice. METHODS/STUDY POPULATION: Ascending aortas from male and female FBN1mgR/mgR mice and their wild type littermates were assessed every 4 weeks from 6 to 18 weeks of age by ultrasound. Measurements were taken luminal edge to luminal edge in diastole. At termination, aortas were harvested for RT-PCR analysis of extracellular matrix genes. Aortas were serially sectioned and elastin fragmentation was imaged by auto-fluorescence. RESULTS/ANTICIPATED RESULTS: At 12 weeks of age, differences of aortic diameters between male and female FBN1mgR/mgR mice were significantly different (2.24±0.43 vs. 1.57±0.22 mm; p=0.002), while there were no significant differences between sexes of wild type littermates (1.29±0.13 vs. 1.23±0.08 mm; p=0.71). Male sex was associated with increased elastin but not fibrillin-1 mRNA expression. Ascending aortas from male and female FBN1mgR/mgR mice significantly differed in the degree of elastin fragmentation (2.76 vs. 1.85 breaks/ 100 µm aorta; p=0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Sexual dimorphism of thoracic aortic dilation observed in human TAA patients was recapitulated in the fibirllin-1 hypomorphic mouse model of syndromic thoracic aortic aneurysms. Differences in this mouse model could be explained by the differential expression of extracellular matrix genes.
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Kozlov, B. N., D. S. Panfilov, E. L. Sonduev y V. L. Lukinov. "Predictors of early adverse events after ascending aortic replacement". Siberian Journal of Clinical and Experimental Medicine 37, n.º 2 (14 de julio de 2022): 65–73. http://dx.doi.org/10.29001/2073-8552-2022-37-2-65-73.
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Objective. The aim of this study was to identify predictors of adverse events after ascending aortic replacement for the aortic aneurysms in the early postoperative period.Material and Methods. The analysis included 151 patients with ascending aortic aneurysm who underwent non-hemiarch or hemiarch repair. The following adverse outcomes were selected: postoperative delirium, respiratory failure, bleeding, multiple organ dysfunction syndrome, and in-hospital mortality. Predictors of adverse clinical events were identified by constructing uni- and multivariate logistic regression.Results. Significant predictors of early outcomes and mortality after ascending aortic replacement were as follows: female gender, atrial fibrillation, low glomerular filtration rate, chronic obstructive pulmonary disease, aortic root repair, multiple organ dysfunction, duration of cardiac arrest, operation time, and reoperation for bleeding.Conclusions. The risk factors of adverse outcomes after ascending aortic replacement were decreased kidney function, atrial fibrillation, female gender, aortic root repair, and increased duration of cardiac arrest and operation time.
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Kozlov, B. N., D. S. Panfilov, E. L. Sonduev y V. L. Lukinov. "Predictors of early adverse events after ascending aortic replacement". Siberian Journal of Clinical and Experimental Medicine 37, n.º 1 (9 de abril de 2022): 108–17. http://dx.doi.org/10.29001/2073-8552-2022-37-1-108-117.
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Objective. The aim of this study was to identify predictors of adverse events after ascending aortic replacement for the aortic aneurysms in the early postoperative period.Material and Methods. The analysis included 151 patients with ascending aortic aneurysm who underwent non-hemiarch or hemiarch repair. The following adverse outcomes were selected: postoperative delirium, respiratory failure, bleeding, multiple organ dysfunction syndrome, and in-hospital mortality. Predictors of adverse clinical events were identified by constructing uni- and multivariate logistic regression.Results. Significant predictors of early outcomes and mortality after ascending aortic replacement were as follows: female gender, atrial fibrillation, low glomerular filtration rate, chronic obstructive pulmonary disease, aortic root repair, multiple organ dysfunction, duration of cardiac arrest, operation time, and reoperation for bleeding.Conclusions. The risk factors of adverse outcomes after ascending aortic replacement were decreased kidney function, atrial fibrillation, female gender, aortic root repair, and increased duration of cardiac arrest and operation time.
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Kozlov, B. N., D. S. Panfilov, E. L. Sonduev y V. L. Lukinov. "Ascending aortic aneurysm: propensity score matching analysis of hemiarch and non-hemiarch replacement". Russian Journal of Cardiology 25, n.º 10 (18 de noviembre de 2020): 3887. http://dx.doi.org/10.15829/1560-4071-2020-3887.
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Aim. To compare the shortand medium-term outcomes of hemiarch and nonhemiarch replacement for ascending aortic aneurysm (AAA).Material and methods. The study included 151 patients with non-syndromic AAA who underwent an elective replacement. Patients were divided into two groups: group 1 (non-hemiarch, n=40) — standard ascending aortic replacement; group 2 (hemiarch, n=111) — ascending aortic replacement with the hemiarch anastomosis in conditions of moderate hypothermia and circulatory arrest with unilateral antegrade cerebral perfusion. To eliminate systematic differences between the compared groups, the propensity score matching (PSM) method was used.Results. Before PSM, there were no significant intergroup differences in the incidence of neurological complications, myocardial infarction, prolonged ventilation, or acute kidney injury. Bleeding-related reoperation rates and hospital mortality significantly differed between groups. After pseudo-randomization between the non-hemiarch and hemiarch groups, there were no significant differences in the incidence of neurological events, myocardial infarction, prolonged ventilation, reoperations for bleeding, acute renal injury, and hospital mortality. Median-term survival and freedom from aortic reoperations also did not show significant intergroup differences.Conclusion. Hemiarch replacement for AAA does not lead to an increase in the incidence of postoperative complications, as well as the risk of shortand mediumterm mortality compared with non-hemiarch.
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Shah, Asad A. "Epigenetic Profiling Identifies Novel Genes for Ascending Aortic Aneurysm Formation with Bicuspid Aortic Valves". Heart Surgery Forum 18, n.º 4 (1 de septiembre de 2015): 134. http://dx.doi.org/10.1532/hsf.1247.
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<p><strong>Background: </strong>Bicuspid aortic valves predispose to ascending aortic aneurysms, but the mechanisms underlying this aortopathy remain incompletely characterized. We sought to identify epigenetic pathways predisposing to aneurysm formation in bicuspid patients.</p><p><strong>Methods: </strong>Ascending aortic aneurysm tissue samples were collected at the time of aortic replacement in subjects with bicuspid and trileaflet aortic valves. Genome-wide DNA methylation status was determined on DNA from tissue using the Illumina 450K methylation chip, and gene expression was profiled on the same samples using Illumina Whole-Genome DASL arrays. Gene methylation and expression were compared between bicuspid and trileaflet individuals using an unadjusted Wilcoxon rank sum test. </p><p><strong>Results: </strong>Twenty-seven probes in 9 genes showed significant differential methylation and expression (P<5.5x10<sup>-4</sup>). The top gene was protein tyrosine phosphatase, non-receptor type 22 (<em>PTPN22</em>), which was hypermethylated (delta beta range: +15.4 to +16.0%) and underexpressed (log 2 gene expression intensity: bicuspid 5.1 vs. trileaflet 7.9, P=2x10<sup>-5</sup>) in bicuspid patients, as compared to tricuspid patients. Numerous genes involved in cardiovascular development were also differentially methylated, but not differentially expressed, including <em>ACTA2</em> (4 probes, delta beta range: -10.0 to -22.9%), which when mutated causes the syndrome of familial thoracic aortic aneurysms and dissections</p><p><strong>Conclusions: </strong>Using an integrated, unbiased genomic approach, we have identified novel genes associated with ascending aortic aneurysms in patients with bicuspid aortic valves, modulated through epigenetic mechanisms. The top gene was <em>PTPN22</em>, which is involved in T-cell receptor signaling and associated with various immune disorders. These differences highlight novel potential mechanisms of aneurysm development in the bicuspid population.</p>
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Monda, Emanuele, Michele Lioncino, Federica Verrillo, Marta Rubino, Martina Caiazza, Alfredo Mauriello, Natale Guarnaccia et al. "The Role of Genetic Testing in Patients with Heritable Thoracic Aortic Diseases". Diagnostics 13, n.º 4 (17 de febrero de 2023): 772. http://dx.doi.org/10.3390/diagnostics13040772.
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Heritable thoracic aortic disease (HTAD) is a term used to define a large group of disorders characterized by the occurrence of aortic events, mainly represented by aneurysm or dissection. These events generally involve the ascending aorta, although the involvement of other districts of the aorta or peripheral vessels may occur. HTAD can be classified as non-syndromic if the disorder is limited to the aorta, and syndromic when associated with extra-aortic features. About 20–25% of patients with non-syndromic HTAD exhibit a family history of aortic disease. Thus, a careful clinical evaluation of the proband and the first-degree family members is required to differentiate familial and sporadic cases. Genetic testing is essential since it allows confirmation of the etiological diagnosis of HTAD (particularly in patients with a significant family history) and may guide family screening. In addition, genetic diagnosis significantly impacts patients’ management since the different conditions significantly differ with respect to natural history and treatment strategies. The prognosis in all HTADs is determined by the progressive dilation of the aorta, potentially leading to acute aortic events, such as dissection or rupture. Moreover, the prognosis varies according to the underlying genetic mutations. This review aims to describe the clinical characteristics and natural history of the most common HTADs, with particular emphasis on the role of genetic testing in risk stratification and management.
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Morgant, Marie-Catherine, Siyu Lin, Diana Marin-Castrillon, Chloé Bernard, Aline Laubriet, Alexandre Cochet, Alain Lalande y Olivier Bouchot. "Comparison of two techniques (in vivo and ex-vivo) for evaluating the elastic properties of the ascending aorta: Prospective cohort study". PLOS ONE 16, n.º 9 (13 de septiembre de 2021): e0256278. http://dx.doi.org/10.1371/journal.pone.0256278.
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Introduction Aneurysms of the ascending aorta (AA) correspond to a dilatation of the ascending aorta that progressively evolves over several years. The main complication of aneurysms of the ascending aorta is type A aortic dissection, which is associated with very high rates of morbidity and mortality. Prophylactic ascending aorta replacement guidelines are currently based on maximal AA diameter. However, this criterion is imperfect. Stretching tests on the aorta carried out ex-vivo make it possible to determine the elastic properties of healthy and aneurysmal aortic fragments (tension test, resistance before rupture). For several years now, cardiac magnetic resonance imaging (MRI) has provided another means of evaluating the elastic properties of the aorta. This imaging technique has the advantage of being non-invasive and of establishing aortic compliance (local measurement of stiffness) without using contrast material by measuring the variation of the aortic surface area during the cardiac cycle, and pulse wave velocity (overall stiffness of the aorta). Materials and methods Prospective single-center study including 100 patients with ascending aortic aneurysm requiring surgery. We will perform preoperative cine-MRI and biomechanical laboratory stretching tests on aortic samples collected during the cardiac procedure. Images will be acquired with a 3T MRI with only four other acquisitions in addition to the conventional protocol. These additional sequences are a Fast Low Angle Shot (FLASH)-type sequence performed during a short breath-hold in the transverse plane at the level of the bifurcation of the pulmonary artery, and phase-contrast sequences that encodes velocity at the same localization, and also in planes perpendicular to the aorta at the levels of the sino-tubular junction and the diaphragm for the descending aorta. For ex-vivo tests, the experiments will be carried out by a biaxial tensile test machine (ElectroForce®). Each specimen will be stretched with 10 times of 10% preconditioning and at a rate of 10 mm/min until rupture. During the experiment, the tissue is treated under a 37°C saline bath. The maximum elastic modulus from each sample will be calculated. Results The aim of this study is to obtain local patient-specific elastic modulus distribution of the ascending aorta from biaxial tensile tests and to assess elastic properties of the aorta using MRI, then to evaluate the correlation between biaxial tests and MRI measurements. Discussion Our research hypothesis is that there is a correlation between the evaluation of the elastic properties of the aorta from cardiac MRI and from stretching tests performed ex-vivo on aorta samples collected during ascending aorta replacement.
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Kravchenko, Vitalii І. "Immediate and Long-Term Results of Treatment of Aneurysms of Ascending Aorta and Aortic Arch and Substantiation of Tactical Approaches to the Treatment Based on the Obtained Results". Ukrainian Journal of Cardiovascular Surgery, n.º 3 (44) (21 de septiembre de 2021): 69–75. http://dx.doi.org/10.30702/ujcvs/21.4409/k.046-69-75.
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Acute aortic dissection is a formidable disease. Its prevalence increases due to the population aging, as well as wider awareness of physicians about this pathology.
The aim. To analyze immediate and long-term results of surgical treatment of aneurysms of ascending aorta and aortic arch and to determine optimal methods of correction of these lesions in order to improve the results of surgical treatment.
Materials and methods. This was a comparative analysis of immediate and long-term treatment outcomes in 419 patients with aneurysms of ascending aorta and aortic arch. A comparative analysis of the results of treatment of two groups of patients was performed: the comparison group of 157 people operated before 2013, and the main group of 262 patients operated since 2013 using modified methods of aortic surgery.
Results. The study showed significant reduction in the left ventricular dilatation according to echocardiography and satisfactory postoperative course in patients of both groups. Patients with valve-sparing aortic prosthetics had better results than those who underwent valve replacement surgery. Hospital mortality decreased from 17.2% to 5.3%.
Analysis of long-term results showed that supracoronary aortic prosthetics with aortic valve plasty and elimination of the intimal tear zone make it possible to carry out effective aortic reconstruction. Due to events in the long run, regular lifelong monitoring is required.
The analysis also showed that individualized approach to the choice of surgical tactics for the correction of aortic insufficiency in patients with aortic root and ascending aortic pathology allows to achieve comparable results in the immediate and long-term follow-up. Despite the complexity of the applied correction methods, the developed methods of surgical treatment of ascending aortic aneurysm (AAA) and aortic arch aneurysm and methods of protection of brain and visceral organs allowed to keep hospital mortality and the number of complications at the same level corresponding to one of the best world results. This gives hope for a good result in the long-term follow-up.
Conclusions. Aneurysm of ascending aorta and aortic arch is a formidable life-threatening disease, and its only non-alternative treatment option is surgery. The optimized approach to the treatment of patients in the main group allowed to obtain better immediate and long-term results of surgical treatment and reduce postoperative complications from 34.4% to 8.4% and hospital mortality from 17.2% to 5.3%. Comparative analysis of long-term results in the studied groups showed more encouraging indicators of quality of life and life expectancy in patients when using modified surgical techniques, protection of the brain and visceral organs. We hope to get a final assessment of these data in the further study of the condition of these patients in the long-term follow-up.
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Khoynezhad, Ali. "The timing of elective ascending aortic aneurysm replacement for non-syndromic patients and the implication of bicuspid aortic valve-related aortopathy". Journal of Thoracic Disease 8, n.º 12 (diciembre de 2016): E1651—E1654. http://dx.doi.org/10.21037/jtd.2016.12.19.
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Zhou, Zhen, Alana C. Cecchi, Siddharth K. Prakash y Dianna M. Milewicz. "Risk Factors for Thoracic Aortic Dissection". Genes 13, n.º 10 (7 de octubre de 2022): 1814. http://dx.doi.org/10.3390/genes13101814.
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Thoracic aortic aneurysms involving the root and/or the ascending aorta enlarge over time until an acute tear in the intimal layer leads to a highly fatal condition, an acute aortic dissection (AAD). These Stanford type A AADs, in which the tear occurs above the sinotubular junction, leading to the formation of a false lumen in the aortic wall that may extend to the arch and thoracoabdominal aorta. Type B AADs originate in the descending thoracic aorta just distal to the left subclavian artery. Genetic variants and various environmental conditions that disrupt the aortic wall integrity have been identified that increase the risk for thoracic aortic aneurysms and dissections (TAD). In this review, we discuss the predominant TAD-associated risk factors, focusing primarily on the non-genetic factors, and discuss the underlying mechanisms leading to TAD.
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Pérez-García, Carlos Nicolás, Carmen Olmos, David Vivas, Carlos Ferrera, Daniel García-Arribas, Daniel Enríquez-Vázquez, Manuel Carnero-Alcázar et al. "IgG4-aortitis among thoracic aortic aneurysms". Heart 105, n.º 20 (21 de mayo de 2019): 1583–89. http://dx.doi.org/10.1136/heartjnl-2018-314499.
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ObjectiveThe incidence of aortitis in patients with thoracic aortic diseases is not well established. The aim of this study was to analyse the frequency and clinical course of patients with aortitis in a surgical series.Methods320 consecutive patients with ascending aorta/aortic arch aneurysm or acute aortic syndrome who underwent surgery from 2012 to 2017 in a single tertiary referral hospital were retrospectively reviewed. Epidemiological data, clinical course and variables related to diagnosis, treatment and follow-up were collected from patients with histologically proven aortitis.ResultsFrom 320 examined aortic samples, 279 (87.2%) thoracic aneurysms and 41 acute aortic syndromes (12.8%), 9 (2.8%) were aortitis: 3 cases of Takayasu’s arteritis, 3 of IgG4-related aortitis, 2 of giant cell, and 1 classified as idiopathic. Median age at surgery was 53.4 (51–69.2) years and six cases were female. Seven patients presented with non-specific symptoms and the diagnosis was made at pathology. Surgery was elective in eight patients and emergent in one case of IgG4-related aortitis. 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) was performed for disease extension study and as a monitoring technique during the follow-up of five patients, with just one case performed presurgically. All the patients with IgG4-related disease showed extrathoracic aortic involvement. There were no deaths, neither in-hospital nor during the 1.7 years of median follow-up.ConclusionsIn surgically treated thoracic aorta pathology, the frequency of aortitis is low; IgG4-related disease is among the most common aetiologies with a frequency similar to other types of aortitis, such as Takayasu’s and giant cell arteritis, and clinical manifestations are non-specific making presurgical diagnosis difficult. 18F-FDG PET/CT allows a better assessment of disease extension and therapeutic response. Surgery can be successfully performed and corticosteroid therapy ensures a good mid-term follow-up.
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Velasco, Juan J., Yupeng Li, Bulat A. Ziganshin, Mohammad A. Zafar, John A. Rizzo, Deqiong Ma, Hui Zang, Asanish Kalyanasundaram y John A. Elefteriades. "KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection". Genes 14, n.º 2 (18 de enero de 2023): 252. http://dx.doi.org/10.3390/genes14020252.
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Background: KIF6 (kinesin family member 6), a protein coded by the KIF6 gene, serves an important intracellular function to transport organelles along microtubules. In a pilot study, we found that a common KIF6 Trp719Arg variant increased the propensity of thoracic aortic aneurysms (TAA) to suffer dissection (AD). The present study aims for a definite investigation of the predictive ability of KIF6 719Arg vis à vis AD. Confirmatory findings would enhance natural history prediction in TAA. Methods: 1108 subjects (899 aneurysm and 209 dissection patients) had KIF6 719Arg variant status determined. Results: The 719Arg variant in the KIF6 gene correlated strongly with occurrence of AD. Specifically, KIF6 719Arg positivity (homozygous or heterozygous) was substantially more common in dissectors (69.8%) than non-dissectors (58.5%) (p = 0.003). Odds ratios (OR) for suffering aortic dissection ranged from 1.77 to 1.94 for Arg carriers in various dissection categories. These high OR associations were noted for both ascending and descending aneurysms and for homozygous and heterozygous Arg variant patients. The rate of aortic dissection over time was significantly higher for carriers of the Arg allele (p = 0.004). Additionally, Arg allele carriers were more likely to reach the combined endpoint of dissection or death (p = 0.03). Conclusions: We demonstrate the marked adverse impact of the 719Arg variant of the KIF6 gene on the likelihood that a TAA patient will suffer aortic dissection. Clinical assessment of the variant status of this molecularly important gene may provide a valuable “non-size” criterion to enhance surgical decision making above and beyond the currently used metric of aortic size (diameter).
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Gasiulė, Stankevičius, Patamsytė, Ražanskas, Žukovas, Kapustina, Žaliaduonytė, Benetis, Lesauskaitė y Vilkaitis. "Tissue-Specific miRNAs Regulate the Development of Thoracic Aortic Aneurysm: the Emerging Role of KLF4 Network". Journal of Clinical Medicine 8, n.º 10 (3 de octubre de 2019): 1609. http://dx.doi.org/10.3390/jcm8101609.
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MicroRNAs (miRNAs) are critical regulators of the functional pathways involved in the pathogenesis of cardiovascular diseases. Understanding of the disease-associated alterations in tissue and plasma will elucidate the roles of miRNA in modulation of gene expression throughout development of sporadic non-syndromic ascending thoracic aortic aneurysm (TAA). This will allow one to propose relevant biomarkers for diagnosis or new therapeutic targets for the treatment. The high-throughput sequencing revealed 20 and 17 TAA-specific miRNAs in tissue and plasma samples, respectively. qRT-PCR analysis in extended cohort revealed sex-related differences in miR-10a-5p, miR-126-3p, miR-155-5p and miR-148a-3p expression, which were the most significantly dysregulated in TAA tissues of male patients. Unexpectedly, the set of aneurysm-related miRNAs in TAA plasma did not resemble the tissue signature suggesting more complex organism response to the disease. Three of TAA-specific plasma miRNAs were found to be restored to normal level after aortic surgery, further signifying their relationship to the pathology. The panel of two plasma miRNAs, miR-122-3p, and miR-483-3p, could serve as a potential biomarker set (AUC = 0.84) for the ascending TAA. The miRNA-target enrichment analysis exposed TGF-β signaling pathway as sturdily affected by abnormally expressed miRNAs in the TAA tissue. Nearly half of TAA-specific miRNAs potentially regulate a key component in TGF-β signaling: TGF-β receptors, SMADs and KLF4. Indeed, using immunohistochemistry analysis we detected increased KLF4 expression in 27% of TAA cells compared to 10% of non-TAA cells. In addition, qRT-PCR demonstrated a significant upregulation of ALK1 mRNA expression in TAA tissues. Overall, these observations indicate that the alterations in miRNA expression are sex-dependent and play an essential role in TAA via TGF-β signaling.
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Forte, Amalia, Umberto Galderisi, Marilena Cipollaro, Marisa De Feo y Alessandro Della Corte. "Epigenetic regulation of TGF-β1 signalling in dilative aortopathy of the thoracic ascending aorta". Clinical Science 130, n.º 16 (7 de julio de 2016): 1389–405. http://dx.doi.org/10.1042/cs20160222.
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The term ‘epigenetics’ refers to heritable, reversible DNA or histone modifications that affect gene expression without modifying the DNA sequence. Epigenetic modulation of gene expression also includes the RNA interference mechanism. Epigenetic regulation of gene expression is fundamental during development and throughout life, also playing a central role in disease progression. The transforming growth factor β1 (TGF-β1) and its downstream effectors are key players in tissue repair and fibrosis, extracellular matrix remodelling, inflammation, cell proliferation and migration. TGF-β1 can also induce cell switch in epithelial-to-mesenchymal transition, leading to myofibroblast transdifferentiation. Cellular pathways triggered by TGF-β1 in thoracic ascending aorta dilatation have relevant roles to play in remodelling of the vascular wall by virtue of their association with monogenic syndromes that implicate an aortic aneurysm, including Loeys–Dietz and Marfan's syndromes. Several studies and reviews have focused on the progression of aneurysms in the abdominal aorta, but research efforts are now increasingly being focused on pathogenic mechanisms of thoracic ascending aorta dilatation. The present review summarizes the most recent findings concerning the epigenetic regulation of effectors of TGF-β1 pathways, triggered by sporadic dilative aortopathy of the thoracic ascending aorta in the presence of a tricuspid or bicuspid aortic valve, a congenital malformation occurring in 0.5–2% of the general population. A more in-depth comprehension of the epigenetic alterations associated with TGF-β1 canonical and non-canonical pathways in dilatation of the ascending aorta could be helpful to clarify its pathogenesis, identify early potential biomarkers of disease, and, possibly, develop preventive and therapeutic strategies.
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Gaibazzi, Nicola, Domenico Tuttolomondo, Francesco Nicolini, Alessandro Tafuni, Daniele Sartorio, Chiara Martini, Francesco Maestri, Alan Gallingani, Massimo De Filippo y Domenico Corradi. "The Histopathological Correlate of Peri-Vascular Adipose Tissue Attenuation on Computed Tomography in Surgical Ascending Aorta Aneurysms: Is This a Measure of Tissue Inflammation?" Diagnostics 11, n.º 10 (29 de septiembre de 2021): 1799. http://dx.doi.org/10.3390/diagnostics11101799.
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On computed tomography (CT) imaging, a peri-vascular adipose tissue attenuation (pVAT) measure has been proposed as a non-invasive correlate of inflammation in the coronary artery vessels, and a single research group provided histopathological demonstration of this radiological/pathological correspondence. Our group has shown that patients with surgical-grade ascending aorta (AA) aneurysm display higher pVAT compared with patients with smaller aneurysms or normal AA. Based on histopathological studies on coronary arteries, we speculated that this correlation may be related to a non-otherwise specified aortic inflammatory process. However, since adipose tissue around the AA is often scant, and there are no histopathological studies confirming such hypothesized association between higher pVAT and inflammation around the AA, we cannot exclude that this pVAT change is secondary to different mechanisms, unrelated to the actual presence of peri-vascular inflammation. We performed a retrospective clinical/radiological/pathological study in 78 patients who underwent AA surgery with the aim to correlate pre-operatory pVAT on CT with histopathological findings from the surgical specimens. Histopathological review and immunohistochemistry were performed on the surgical aortic samples. The AA adventitial/periadventitial adipose tissue had higher pVAT by an increasing collagen fiber deposition, which progressively makes the fat hypotrophic and, in the late stages of this process, it replaces the normal soft tissue composition in this location. In the ascending aorta, pVAT on CT imaging is probably not a proxy for the presence of current vascular inflammation, although it may track changes involving the progressive substitution of perivascular adipose cells by higher-pVAT tissues, mainly fibrotic replacement.
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von Tengg-Kobligk, Hendrik, Dittmar Böckler, Tania M. Jose, Marika Ganten, Osos Kotelis, Simon Nagel, Frederik L. Giesel et al. "Feeding Arteries of the Spinal Cord at CT Angiography before and after Thoracic Aortic Endografting". Journal of Endovascular Therapy 14, n.º 5 (octubre de 2007): 639–49. http://dx.doi.org/10.1177/152660280701400507.
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Purpose: To study the visualization of spinal cord feeding arteries in patients with complex thoracic aortic pathology undergoing endovascular aortic repair (EVAR) using an optimized protocol for multislice computed tomographic angiography (MSCTA). Methods: Eighteen consecutive patients (13 men; mean age 63 years, range 45–79) with aortic type B dissections (n=5), chronic expanding aortic dissections (n=5), thoracic aortic aneurysms (n=6), or penetrating aortic ulcers (n=2) underwent 16-slice CTA before and after (mean interval 9 days) EVAR. Pulse rate and neurological status were documented. Quantitative density measurements were taken at regions of interest (ROI) in the ascending thoracic aorta and at the level of the diaphragm. Two experienced radiologists qualitatively assessed the posterior intercostal arteries (PIA; fully visible, partially visible, non-visible), dorsal branches (DB; visible/non-visible), and artery of Adamkiewicz (AKA; visible/non-visible) on multiplanar reformations and maximum intensity projection reconstructions. Results: MSCTA was performed successfully in 17/18 patients before and after EVAR (1 patient was excluded after EVAR owing to rising creatinine levels). Before EVAR, MSCTA revealed 197/203 PIAs within the stented area, of which 179 were fully and 18 partially visible. No significant (p=0.37) difference was noted for overall PIA detection within the stented area on post-EVAR MSCTA (185/203 PIA), although only 124 were fully and 61 partially visible. Similar results were obtained for DB visualization. The AKA were seen in 10/17 patients pre EVAR and 9/17 post EVAR. In 2 patients, the AKA was localized within the stented aortic segment. ROI analysis revealed contrast densities of 427±89 HU and 398±84 HU on pre- and post-EVAR MSCTA, respectively. No neurological events were observed. Conclusion: The majority of posterior intercostal arteries and dorsal branches remain open after EVAR due to retrograde perfusion. High-resolution MSCTA permits accurate pre-and post-EVAR visualization of spinal cord feeding arteries in patients with thoracic aortic pathology.
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Mizuno, Tomohiro, Tsuyoshi Hachimaru, Tatsuki Fujiwara, Kiyotoshi Oishi, Masashi Takeshita, Masafumi Yashima, Yushi Okumura, Eiki Nagaoka, Keiji Oi y Hirokuni Arai. "One-Stage Hybrid Total Aortic Arch and Descending Thoracic Aortic Repair is a Safe and Secure Procedure With Less Postoperative Complications for Extended Aortic Arch Aneurysms". Journal of Endovascular Therapy 29, n.º 2 (28 de septiembre de 2021): 204–14. http://dx.doi.org/10.1177/15266028211047954.
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Purpose Hybrid aortic arch repair (HAR) has been implemented for extended aortic arch and descending thoracic aortic disease since 2012 in our institution. This study aimed to estimate the early and mid-term efficacy and safety of HAR. Materials and Methods From 2007 to 2019, 56 patients underwent HAR for extended aortic arch disease, and 75 patients underwent total arch replacement (TAR) for arch-limited disease. HAR comprises 3 procedures: replacement of the aorta, reconstruction of all arch vessels, and thoracic endovascular aortic repair (TEVAR) from zone 0 to the descending aorta after cardiopulmonary bypass is off in 1 stage. The type II-1 HAR procedure, in which the ascending aorta and aortic arch distal to the brachiocephalic artery are replaced, was the most frequently selected procedure (40/56 patients). The outcomes of the type II-1 HAR procedure were compared with those of TAR using the Cox regression analysis. Results The median follow-up period was 36 months. In HAR, the operative mortality, in-hospital mortality, and postoperative permanent neurological deficits were not observed. The paraplegia rate was 1.8%. TEVAR-related complications occurred in 3 patients. Among the patients with non-ruptured atherosclerotic aortic arch aneurysm (31 type II-1 HAR patients and 36 TAR patients, the postoperative respiratory support time in those who underwent type II-1 HAR was quicker than in those who underwent TAR (p<0.01). The rate of 6 year freedom from all-cause death in type II-1 HAR (83.1%) was numerically higher than that in TAR (74.7%), and the rate of 6 year freedom from surgery-related complications in type II-1 HAR (90.3%) was numerically lower than that in TAR (96.9%) due to the occurrence of TEVAR-related complications, and the rate of 6 year freedom from reintervention to the descending thoracic aorta in type II-1 HAR (100%) seemed to be better than that in TAR (83.7%). However, Cox regression analysis did not reveal any statistical difference between the 2 procedures. Conclusions HAR, especially the type II-1 procedure, can treat extended aortic arch disease with acceptable survival outcomes. The development of TEVAR technology will further improve the outcomes of HAR in the future.
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Gelsomino, Sandro, Romeo Frassani, Giorgio Morocutti, Gianluca Masullo, Paolo Da Col, Leonardo Spedicato, Lorenzo Porreca y Ugolino Livi. "A Short-Term Experience with the Tirone David I Valve Sparing Operation for the Treatment of Aneurysms of the Ascending Aorta and Aortic Root". Cardiovascular Surgery 11, n.º 3 (junio de 2003): 189–94. http://dx.doi.org/10.1177/096721090301100303.
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Aim The aim of this report is to summarize our experience with the Tirone David I technique over a 4-year period. Methods Since 1997 15 patients were operated on using this surgical procedure. Of the patients, nine were male (60%) and six (40%) female. Ages ranged from 23 to 75 years (mean 62.1 ± 17.2 years). The underlying disease was chronic aneurysm of the ascending aorta or root in 13 (86.6%) and chronic dissection in two (13.4%). Four patients (26.6%) had skeletal manifestations of Marfan's syndrome. Additional cardiac procedures were performed in two patients (13.4%). Mean follow-up time was 26.6 ± 11.2 months (range 7–50 months). Results There were no early deaths. Postoperative non-fatal complications occurred in two (13.3%) patients. There was no valve-related late death occurring 6 months after operation. Actuarial survival was 0.94 ± 0.07 at 4 years; 4-year freedom from reoperation was 0.91 ± 0.07. The probability of needing reoperation was 8 ± 0.9%. There were no instances of infective endocarditis or thromboembolic complications. At the end of the follow-up period, trivial or no aortic regurgitation was demonstrated in 57.1%, mild in 42.9% and no patient had an insufficiency graded ≥moderate. Echocardiography showed early postoperative reduction in left ventricular end-systolic and end-diastolic dimensions, which was maintained at follow-up controls. Conclusions The Tirone David I procedure showed good early results, which encourage further use of this type of repair. However, further larger studies and long-term results are necessary for a definite judgment on this operative method.
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Zhang, Jing, Guangpu Fan, Hui Zhao, Xu Wang, Zhiwei Wang, Peide Zhang y Wei Wang. "Dilatation of the initially non-aneurysmal ascending aorta after replacement of a bicuspid versus tricuspid aortic valve". Journal of International Medical Research 44, n.º 6 (6 de agosto de 2016): 1222–33. http://dx.doi.org/10.1177/0300060516642306.
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Objective To compare the aortic diameter after isolated aortic valve replacement (AVR) in patients with a bicuspid (BAV) or tricuspid aortic valve (TAV) and an initially normal ascending aorta. Methods Patients with an ascending aortic diameter of < 45 mm who had undergone isolated AVR were studied. Ultrasonic cardiographic measurements of the ascending aortic diameter made pre- and postoperatively and follow-up data concerning adverse aortic events and death were analyzed. Results A total of 613 patients were included in this retrospective study; of these, 211 had a BAV and 402 had a TAV. In both groups, the ascending aorta significantly expanded but was non-aneurysmal during follow-up; however, the difference between the two groups was not significant. Cox regression analysis showed no significant effect associated with the presence of a BAV on adverse aortic events or death. Conclusion Dilatation of the ascending aorta was observed after AVR in both groups, but was not more pronounced in patients with a BAV. Long-term follow-up for ascending aortic aneurysm is necessary after AVR in both patients with a BAV and those with a TAV.
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Oike, Yuichi, Yasuhiro Ito, Koichi Hamada, Xiu-Qin Zhang, Keishi Miyata, Fumio Arai, Tomohisa Inada et al. "Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells". Blood 100, n.º 4 (15 de agosto de 2002): 1326–33. http://dx.doi.org/10.1182/blood.v100.4.1326.h81602001326_1326_1333.
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Although the cellular and molecular mechanisms governing angiogenesis are only beginning to be understood, signaling through endothelial-restricted receptors, particularly receptor tyrosine kinases, has been shown to play a pivotal role in these events. Recent reports show that EphB receptor tyrosine kinases and their transmembrane-type ephrin-B2 ligands play essential roles in the embryonic vasculature. These studies suggest that cell-to-cell repellent effects due to bidirectional EphB/ephrin-B2 signaling may be crucial for vascular development, similar to the mechanism described for neuronal development. To test this hypothesis, we disrupted the precise expression pattern of EphB/ephrin-B2 in vivo by generating transgenic (CAGp-ephrin-B2 Tg) mice that express ephrin-B2 under the control of a ubiquitous and constitutive promoter, CMV enhancer-β-actin promoter-β-globin splicing acceptor (CAG). These mice displayed an abnormal segmental arrangement of intersomitic vessels, while such anomalies were not observed in Tie-2p-ephrin-B2 Tg mice in which ephrin-B2 was overexpressed in only vascular endothelial cells (ECs). This finding suggests that non-ECs expressing ephrin-B2 alter the migration of ECs expressing EphB receptors into the intersomitic region where ephrin-B2 expression is normally absent. CAGp-ephrin-B2 Tg mice show sudden death at neonatal stages from aortic dissecting aneurysms due to defective recruitment of vascular smooth muscle cells to the ascending aorta. EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells plays an essential role in vasculogenesis, angiogenesis, and vessel maturation.
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Carvajal, Julián Rondón. "Widened mediastinum at elderly: a challenge in the emergency room (ER)". Journal of Lung, Pulmonary & Respiratory Research 9, n.º 4 (30 de diciembre de 2022): 102–5. http://dx.doi.org/10.15406/jlprr.2022.09.00289.
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A widened mediastinum is a feature often seen on a plain chest x-ray. When the mediastinum is greater than 6 to 8 cm, depending on which source, it is noted to be wide. A wide mediastinum has many causes which include thoracic aortic aneurysm of the ascending and proximal descending aorta, aortic dissection of ascending and proximal descending aorta, unfolding of the aorta, passing through traumatic aortic ruptura and non-vascular structural causes, such as hilar lymphadenopathy either infectious or malignant (lymphoma, seminoma, thymoma). At elderly, this finding constitutes a real challenge in the emergency room, which must be interpreted in the light of the hemodynamic condition of the patient, taking into account that in the scenario of chronic aortic syndrome it includes aneurysmal dilatations of the aortic root that can be dissected incompletely, presenting with latent intramural hematoma in ascending aorta until aortic tamponade with secondary obstructive shock.
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D’Amico, Federico, Elena Doldo, Calogera Pisano, Maria Giovanna Scioli, Federica Centofanti, Giulia Proietti, Mattia Falconi et al. "Specific miRNA and Gene Deregulation Characterize the Increased Angiogenic Remodeling of Thoracic Aneurysmatic Aortopathy in Marfan Syndrome". International Journal of Molecular Sciences 21, n.º 18 (19 de septiembre de 2020): 6886. http://dx.doi.org/10.3390/ijms21186886.
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Marfan syndrome (MFS) is a connective tissue disease caused by mutations in the FBN1 gene, leading to alterations in the extracellular matrix microfibril assembly and the early formation of thoracic aorta aneurysms (TAAs). Non-genetic TAAs share many clinico-pathological aspects with MFS and deregulation of some microRNAs (miRNAs) has been demonstrated to be involved in the progression of TAA. In this study, 40 patients undergoing elective ascending aorta surgery were enrolled to compare TAA histomorphological features, miRNA profile and related target genes in order to find specific alterations that may explain the earlier and more severe clinical outcomes in MFS patients. Histomorphological, ultrastructural and in vitro studies were performed in order to compare aortic wall features of MFS and non-MFS TAA. MFS displayed greater glycosaminoglycan accumulation and loss/fragmentation of elastic fibers compared to non-MFS TAA. Immunohistochemistry revealed increased CD133+ angiogenic remodeling, greater MMP-2 expression, inflammation and smooth muscle cell (SMC) turnover in MFS TAA. Cultured SMCs from MFS confirmed higher turnover and α-smooth muscle actin expression compared with non-MFS TAA. Moreover, twenty-five miRNAs, including miR-26a, miR-29, miR-143 and miR-145, were found to be downregulated and only miR-632 was upregulated in MFS TAA in vivo. Bioinformatics analysis revealed that some deregulated miRNAs in MFS TAA are implicated in cell proliferation, extracellular matrix structure/function and TGFβ signaling. Finally, gene analysis showed 28 upregulated and seven downregulated genes in MFS TAA, some of them belonging to the CDH1/APC and CCNA2/TP53 signaling pathways. Specific miRNA and gene deregulation characterized the aortopathy of MFS and this was associated with increased angiogenic remodeling, likely favoring the early and more severe clinical outcomes, compared to non-MFS TAA. Our findings provide new insights concerning the pathogenetic mechanisms of MFS TAA; further investigation is needed to confirm if these newly identified specific deregulated miRNAs may represent potential therapeutic targets to counteract the rapid progression of MFS aortopathy.
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Gomez, Delphine, Ayman Al Haj Zen, Luciano F. Borges, Monique Philippe, Paulo Sampaio Gutierrez, Guillaume Jondeau, Jean-Baptiste Michel y Roger Vranckx. "Syndromic and non-syndromic aneurysms of the human ascending aorta share activation of the Smad2 pathway". Journal of Pathology 218, n.º 1 (mayo de 2009): 131–42. http://dx.doi.org/10.1002/path.2516.
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Zhang, Eryong. "Non-syndromic thoracic aortic aneurysms and dissections-a genetic review". Frontiers in Bioscience 18, n.º 1 (2013): 305. http://dx.doi.org/10.2741/4101.
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Memis, Feyza, Carlijn G. E. Thijssen, Arjen L. Gökalp, Maximiliaan L. Notenboom, Frederike Meccanici, Mohammad Mostafa Mokhles, Roland R. J. van Kimmenade et al. "Elective Ascending Aortic Aneurysm Surgery in the Elderly". Journal of Clinical Medicine 12, n.º 5 (3 de marzo de 2023): 2015. http://dx.doi.org/10.3390/jcm12052015.
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Background. No clear guidelines exist for performing preventive surgery for ascending aortic (AA) aneurysm in elderly patients. This study aims to provide insights by: (1) evaluating patient and procedural characteristics and (2) comparing early outcomes and long-term mortality after surgery between elderly and non-elderly patients. Methods. A multicenter retrospective observational cohort-study was performed. Data was collected on patients who underwent elective AA surgery in three institutions (2006–2017). Clinical presentation, outcomes, and mortality were compared between elderly (≥70 years) and non-elderly patients. Results. In total, 724 non-elderly and 231 elderly patients were operated upon. Elderly patients had larger aortic diameters (57.0 mm (IQR 53–63) vs. 53.0 mm (IQR 49–58), p < 0.001) and more cardiovascular risk factors at the time of surgery than non-elderly patients. Elderly females had significantly larger aortic diameters than elderly males (59.5 mm (55–65) vs. 56.0 mm (51–60), p < 0.001). Short-term mortality was comparable between elderly and non-elderly patients (3.0% vs. 1.5%, p = 0.16). Five-year survival was 93.9% in non-elderly patients and 81.4% in elderly patients (p < 0.001), which are both lower than that of the age-matched general Dutch population. Conclusion. This study showed that in elderly patients, a higher threshold exists to undergo surgery, especially in elderly females. Despite these differences, short-term outcomes were comparable between ‘relatively healthy’ elderly and non-elderly patients.
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Dawson, Ashley, Yanming Li, Yang Li, Pingping Ren, Hernan G. Vasquez, Chen Zhang, Kimberly R. Rebello et al. "Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-β Signaling". Genes 13, n.º 1 (30 de diciembre de 2021): 95. http://dx.doi.org/10.3390/genes13010095.
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The molecular and cellular processes leading to aortic aneurysm development in Marfan syndrome (MFS) remain poorly understood. In this study, we examined the changes of aortic cell populations and gene expression in MFS by performing single-cell RNA sequencing (scRNA seq) on ascending aortic aneurysm tissues from patients with MFS (n = 3) and age-matched non-aneurysmal control tissues from cardiac donors and recipients (n = 4). The expression of key molecules was confirmed by immunostaining. We detected diverse populations of smooth muscle cells (SMCs), fibroblasts, and endothelial cells (ECs) in the aortic wall. Aortic tissues from MFS showed alterations of cell populations with increased de-differentiated proliferative SMCs compared to controls. Furthermore, there was a downregulation of MYOCD and MYH11 in SMCs, and an upregulation of COL1A1/2 in fibroblasts in MFS samples compared to controls. We also examined TGF-β signaling, an important pathway in aortic homeostasis. We found that TGFB1 was significantly upregulated in two fibroblast clusters in MFS tissues. However, TGF-β receptor genes (predominantly TGFBR2) and SMAD genes were downregulated in SMCs, fibroblasts, and ECs in MFS, indicating impairment in TGF-β signaling. In conclusion, despite upregulation of TGFB1, the rest of the canonical TGF-β pathway and mature SMCs were consistently downregulated in MFS, indicating a potential compromise of TGF-β signaling and lack of stimulus for SMC differentiation.
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Ostberg, Nicolai P., Mohammad A. Zafar, Bulat A. Ziganshin y John A. Elefteriades. "The Genetics of Thoracic Aortic Aneurysms and Dissection: A Clinical Perspective". Biomolecules 10, n.º 2 (24 de enero de 2020): 182. http://dx.doi.org/10.3390/biom10020182.
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Thoracic aortic aneurysm and dissection (TAAD) affects many patients globally and has high mortality rates if undetected. Once thought to be solely a degenerative disease that afflicted the aorta due to high pressure and biomechanical stress, extensive investigation of the heritability and natural history of TAAD has shown a clear genetic basis for the disease. Here, we review both the cellular mechanisms and clinical manifestations of syndromic and non-syndromic TAAD. We particularly focus on genes that have been linked to dissection at diameters <5.0 cm, the current lower bound for surgical intervention. Genetic screening tests to identify patients with TAAD associated mutations that place them at high risk for dissection are also discussed.
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Heuts, Samuel, Bouke P. Adriaans, Suzanne Gerretsen, Ehsan Natour, Rein Vos, Emile C. Cheriex, Harry J. G. M. Crijns et al. "Aortic elongation part II: the risk of acute type A aortic dissection". Heart 104, n.º 21 (28 de marzo de 2018): 1778–82. http://dx.doi.org/10.1136/heartjnl-2017-312867.
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ObjectivesProphylactic surgery for prevention of acute type A aortic dissection (ATAAD) is reserved for patients with an ascending aortic aneurysm ≥55 mm. Identification of additional risk predictors is warranted since over 70% of patients presenting with ATAAD have a non-dilated aorta or an aneurysm that would not have met the diameter criterion for preventative surgery. Aim of the study was to evaluate ascending aortic elongation as a risk factor for ATAAD and to compare aortic lengths between ATAAD patients and healthy controls.MethodsAortic lengths and diameters of ATAAD patients were measured on three-dimensional modelled computed tomography and adjusted to predissection dimensions in this cross-sectional single-centre study. Logistic regression was used to evaluate the relation between ATAAD and aortic dimensions. Lengths of different aortic segments were compared with a healthy control group using propensity score matching.ResultsTwo-hundred and fifty patients were included in the study (ATAAD, n=40; controls, n=210). Ascending aortic length and diameter proved to be independent predictors for ATAAD (OR=5.3, CI 2.5 to 11.4, p<0.001 and OR=8.6, CI 2.4 to 31.0, p=0.001). Eighty patients were matched based on propensity scores (ATAAD n=40, controls n=40). The ascending aorta was longer and more dilated in ATAAD patients compared with healthy controls (78.6±8.8 mm vs 68.9±7.2 mm, p<0.001, 34.4 mm ±3.2. vs 39.4 mm ±5.7, p<0.001, respectively). No differences were found in lengths of the aortic arch and descending aorta.ConclusionsAscending aortic length could serve as an independent predictor for ATAAD. Future studies addressing indications for prophylactic surgery should also investigate aortic length.
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Huliyurdurga Srinivasasetty, Natraj Setty, Raghu Thagachagere Ramegowda, Jayashree Kharge, Geetha Bachahalli Krishnanayak, Shivanand S Patil, Varada Raj, Nishanth Kandenahalli Ravindranath y Manjunath Cholenahalli Nanjappa. "Unusual non progressive idiopathic giant ascending aortic aneurysm—A rarity". International Journal of Surgery Case Reports 25 (2016): 203–6. http://dx.doi.org/10.1016/j.ijscr.2016.06.049.
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Tiwari, KK, S. Bevilacqua, A. Salvati, E. Varone, M. Solinas y M. Glauber. "Ascending Aortic Aneurysm, Wandering towards Old Problem with New Insight". Journal of Universal College of Medical Sciences 2, n.º 2 (28 de septiembre de 2014): 49–59. http://dx.doi.org/10.3126/jucms.v2i2.11175.
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Ascending aortic aneurysm is a silent and highly lethal disease. Generally, ascending aorta grows asymptomatically until it dissect or rupture. In case of acute complication mortality is as high as 90%, whereas if treated on time mortality and morbidity decreases significantly. Pathophysiology of the Ascending aortic aneurysm is a complex process. Aorta itself is an organ and it should not be considered merely as a tube transporting blood from heart to the organs. Several non-invasive and invasive imaging methods are available at disposition to diagnose this indolent killer at early stage. However, discrepancies exists about when to operate these patients. Several other methods has been reported to identify these patients at risk of dissection or rupture. Conservative treatment could be used in patients with small aortic diameter, but effectiveness of such approach is under scrutiny. Emerging endovascular treatment using stents should be advocated with caution. Surgical treatment, the gold standard, is recommended for asymptomatic patients with aortic diameter of 5.5cm, whereas 4-4.5cm for patients with Marfan's disease. Postoperative morbidity and mortality has significantly decreased due to better anesthetic management, improved surgical techniques and progress in preoperative and postoperative care. DOI: http://dx.doi.org/10.3126/jucms.v2i2.11175 Journal of Universal College of Medical Sciences (2014) Vol.2(2): 49-59
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Forte, Amalia, Xiaoke Yin, Marika Fava, Ciro Bancone, Marilena Cipollaro, Marisa De Feo, Manuel Mayr, Marjan Jahangiri y Alessandro Della Corte. "Locally different proteome in aortas from patients with stenotic tricuspid and bicuspid aortic valves†". European Journal of Cardio-Thoracic Surgery 56, n.º 3 (25 de febrero de 2019): 458–69. http://dx.doi.org/10.1093/ejcts/ezz032.
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Abstract OBJECTIVES We aimed to compare the intracellular proteome of ascending aortas from patients with stenotic bicuspid (BAV) and tricuspid aortic valves (TAV) to identify BAV-specific pathogenetic mechanisms of aortopathy and to verify the previously reported asymmetric expression of BAV aortopathy [concentrated at the convexity (CVX)] in its ‘ascending phenotype’ form. METHODS Samples were collected from the CVX and concavity sides of non-aneurysmal ascending aortas in 26 TAV and 26 BAV patients undergoing stenotic aortic valve replacement. Aortic lysates were subjected to cellular protein enrichment by subfractionation, and to proteome comparison by 2-dimensional fluorescence difference in-gel electrophoresis. Differentially regulated protein spots were identified by liquid chromatography–tandem mass spectrometry and analysed in silico. Selected results were verified by immunofluorescence and reverse transcription-polymerase chain reaction. RESULTS In BAV samples, 52 protein spots were differentially regulated versus TAV samples at the CVX and 10 spots at the concavity: liquid chromatography–tandem mass spectrometry identified 35 and 10 differentially regulated proteins, respectively. Charge trains of individual proteins (e.g. annexins) suggested the presence of post-translational modifications possibly modulating their activity. At the CVX, 37 of the 52 different protein spots showed decreased expression in BAV versus TAV. The affected biological pathways included those involved in smooth muscle cell contractile phenotype, metabolism and cell stress. CONCLUSIONS The observed differential proteomics profiles may have a significant impact on the pathogenesis of the aortopathy, pointing the way for further studies. At a preaneurysmal stage, an aorta with BAV shows more protein expression changes and potentially more post-translational modifications at the CVX of the ascending aorta than at the concavity, compared to that of TAV.
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Joković, Vuk, Igor Končar, Dragan Knežević, Sasa Sretenović, Dragan Stamenković y Dragan Vulić. "Free floating thrombus in the non-atherosclerotic, non-aneurysmal ascending thoracic aorta: A rare entity". Medicinski casopis 51, n.º 4 (2017): 136–39. http://dx.doi.org/10.5937/mckg51-16433.
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Göbölös, Laszlo, Gurjyot Bajwa, Jehad Ramahi, Pier Carlo Bergonzi y Gopal Bhatnagar. "An Aortic “Supravalvular Shelf” is Not Always Innocuous". New Emirates Medical Journal 1, n.º 1 (21 de febrero de 2020): 17–19. http://dx.doi.org/10.2174/0250688202002021101.
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Supravalvular aortic stenosis is a rare cause of secondary aortic root distension and/or aortic valve regurgitation. Non-syndromic aortic aneurysms may also occur in young adults and can develop silently, representing an asymptomatic, life-threatening condition. Clinicians should, therefore, be alert to the possibility of this uncommon, but potentially serious disease, often first revealed by an imaging modality requested for other indications, even in case of an established, more benign diagnosis.
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Panfilov, D. S., B. A. Bazarbekova, N. O. Panfilova, V. V. Saushkin, E. L. Sonduev, S. I. Sazonova y B. N. Kozlov. "Changes in aortic root dimensions after ascending aortic repair with concomitant aortic valve replacement". Russian Journal of Cardiology 28, n.º 1 (20 de noviembre de 2022): 5198. http://dx.doi.org/10.15829/1560-4071-2023-5198.
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The issue of ascending aortic repair with concomitant aortic valve replacement in pa-tients with ascending aortic aneurysm (AscAA) and aortic valve stenosis is still debatable.Aim. To analyze the dimension changes of the preserved aortic root after simultaneous ascending aorta repair and aortic valve replacement.Material and methods. This retrospective study included 102 patients who, from December 2012 to May 2022, underwent simultaneous aortic valve replacement and ascending aorta repair with hemiarch replacement. Patients were divided into 2 following groups based on the aortic valve morphology: group 1 — patients with bicuspid aortic valve (BAV) and AscAA (n=75), group 2 — patients with tricuspid aortic valve (TAV) and AscAA (n=27). Depending on the presence of aortic root dilatation (maximum diameter (d) >40 mm), each of the groups was additionally stratified into 2 more subgroups as follows: patients without aortic root dilatation (d≤40 mm) and patients with its dilatation (d>40 mm). The dynamics of the aortic root diameter was assessed by computed tomography angiography.Results. The mean follow-up period for patients was 36,2±14,6 months. Survival rate in the BAV+AscAA and TAV+AscAA groups was 96% and 100%, respectively (p=0,380). Freedom from aortic root resurgery was 100% in both study groups. In patients with dilated and non-dilated aortic root of the BAV+AscAA group, an increase in aortic root dimension was noted at a rate of 0,65±0,51 mm/year and 0,32±0,27 mm/year, respectively. In patients of the TAV+AscAA group, a regression in dilated and non-dilated aortic root diameter was observed as follows: 0,93±0,48 mm/year and 0,56±0,43 mm/year, respectively.Conclusion. In patients with AscAA in combination with BAV stenosis after a singlestep surgical intervention, a weak negative dynamics of non-dilated and dilated aortic root is observed in the mid-term follow-up period. In patients with AscAA and TAV, there is involutive alterations of the aortic root dimension during 3-year follow-up.
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Mennander, Ari A., Dylan V. Miller, Kimberly P. Liang, Kenneth J. Warrington, Heidi M. Connolly, Hartzell V. Schaff y Thoralf M. Sundt. "Surgical management of ascending aortic aneurysm due to non-infectious aortitis". Scandinavian Cardiovascular Journal 42, n.º 6 (enero de 2008): 417–24. http://dx.doi.org/10.1080/14017430802023086.
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Chiarini, Anna, Francesco Onorati, Maddalena Marconi, Alessandra Pasquali, Cristina Patuzzo, Anna Malashicheva, Olga Irtyega et al. "Studies on sporadic non-syndromic thoracic aortic aneurysms: 1. Deregulation of Jagged/Notch 1 homeostasis and selection of synthetic/secretor phenotype smooth muscle cells". European Journal of Preventive Cardiology 25, n.º 1_suppl (30 de abril de 2018): 42–50. http://dx.doi.org/10.1177/2047487318759119.
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Background Sporadic non-syndromic thoracic aortic aneurysms (SNSTAAs) are less well understood than familial non-syndromic or syndromic ones. The study aimed at defining the peculiar morphologic and molecular changes occurring in the media layer of SNSTAAs. Design This study was based on a single centre design. Methods Media layer samples taken from seven carefully selected SNSTAAs and seven reference patients (controls) were investigated via quantitative polymerase chain reaction, proteomics-bioinformatics, immunoblotting, quantitative histology, and immunohistochemistry/immunofluorescence. Results In SNSTAAs media, aortic smooth muscle cells numbers were halved due to an apoptotic process coupled with a negligible cell proliferation. Cystathionine γ-lyase was diffusely up-regulated. Surviving aortic smooth muscle cells exhibited diverging phenotypes: in inner- and outer-media contractile cells prevailed, having higher contents of smooth-muscle-α-actin holoprotein (45-kDa) and of caspase-3-cleaved smooth-muscle-α-actin 25-kDa fragments; in mid-media, aortic smooth muscle cells exhibited a synthetic/secretor phenotype, down-regulating vimentin, but up-regulating glial fibrillary acidic protein, trans-Golgi network 46 protein, Jagged1 (172-kDa) holoprotein, and Jagged1’s receptor Notch1. Extracellular soluble Jagged1 (42-kDa) fragments accumulated. Conclusions In SNSTAAs, there is a relentless aortic smooth muscle cells attrition caused by the up-regulated cystathionine γ-lyase. In mid-media, synthetic/secretor aortic smooth muscle cells intensify Jagged1/NOTCH1 signalling in the attempt to counterbalance the weakened aortic wall, due to aortic smooth muscle cells net loss and mechanical stress. Synthetic/secretor aortic smooth muscle cells are apoptosis-prone, and the accruing thrombin-cleaved Jagged1 fragments counteract the otherwise useful effects of Jagged1/NOTCH1 signalling, thus hampering tissue homeostasis/remodelling, and aortic smooth muscle cells adhesion, differentiation, and migration.
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Hiratzka, Loren, Tiffany Hanlon y Katherine Vorpe. "Ascending Aortic Aneurysms < 4.5 cm for Non-syndromic Adults: Very Slow Growth and Low Risk". AORTA, 20 de diciembre de 2022. http://dx.doi.org/10.1055/a-2000-7812.
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Background Current practice guidelines for patients with thoracic aortic aneurysms (TAAs) recommend 6-12-month intervals for surveillance imaging based on growth estimates of 0.10 - 0.42 cm/year gleaned from limited studies which included patients with thoraco-abdominal aneurysms, known acute or chronic aortic dissection, and other syndromic and non-syndromic high risk conditions (TAA-HRC) associated with high-risk for adverse aortic events and death. Objective: Our objective was to determine TAA growth and event-free survival rates for patients with aortic root or mid-ascending diameters <5.0 cm, and without thoraco-abdominal aneurysms, acute or chronic aortic dissection or higher risk syndromic or non-syndromic conditions (TAA-NoHRC). Materials and Methods A retrospective review of patient records and imaging studies was done. Aortic diameter measurements were all performed by the lead author. Results For 197 TAA-NoHRC found incidentally during chest imaging, with 616 chest imaging studies over 868 patient-years, the mean aortic root and mid-ascending aortic growth rates were 0.018 and 0.022 cm/year respectively. Growth rate was significantly lower for aneurysms initially measured at <4.5 cm versus > 4.5 cm at both the aortic root (0.011 vs 0.068 cm/year) and mid-ascending aorta (0.013 vs 0.043 cm/year). Survival free from adverse aortic events (dissection, rupture, surgery) or death at 5 years was 99.5%. Conclusions Adult TAA-NoHRC patients with initial aortic root and/or ascending aortic diameters <5.0 cm, and particularly <4.5 cm, have very low aortic growth and adverse event rates which may permit longer intervals between surveillance imaging, up to 3-5 years, after initial (6-12 month) stability is documented.
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Adriaans, B. P., M. J. F. G. Ramaekers, S. Heuts, H. J. G. M. Crijns, S. C. A. M. Bekkers, J. J. M. Westenberg, H. J. Lamb, J. E. Wildberger y S. Schalla. "Determining the optimal interval for imaging surveillance of ascending aortic aneurysms". Netherlands Heart Journal, 13 de abril de 2021. http://dx.doi.org/10.1007/s12471-021-01564-9.
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Abstract Background Cardiovascular guidelines recommend (bi-)annual computed tomography (CT) or magnetic resonance imaging (MRI) for surveillance of the diameter of thoracic aortic aneurysms (TAAs). However, no previous study has demonstrated the necessity for this approach. The current study aims to provide patient-specific intervals for imaging follow-up of non-syndromic TAAs. Methods A total of 332 patients with non-syndromic ascending aortic aneurysms were followed over a median period of 6.7 years. Diameters were assessed using all available imaging techniques (echocardiography, CT and MRI). Growth rates were calculated from the differences between the first and last examinations. The diagnostic accuracy of follow-up protocols was calculated as the percentage of subjects requiring pre-emptive surgery in whom timely identification would have occurred. Results The mean growth rate in our population was 0.2 ± 0.4 mm/year. The highest recorded growth rate was 2.0 mm/year, while 40.6% of patients showed no diameter expansion during follow-up. Females exhibited significantly higher growth rates than men (0.3 ± 0.5 vs 0.2 ± 0.4 mm/year, p = 0.007). Conversely, a bicuspid aortic valve was not associated with more rapid aortic growth. The optimal imaging protocol comprises triennial imaging of aneurysms 40–49 mm in diameter and yearly imaging of those measuring 50–54 mm. This strategy is as accurate as annual follow-up, but reduces the number of imaging examinations by 29.9%. Conclusions In our population of patients with non-syndromic TAAs, we found aneurysm growth rates to be lower than those previously reported. Yearly imaging does not lead to changes in the management of small aneurysms. Thus, lower imaging frequencies might be a good alternative approach.
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El-Gamel, Adam, Josephine Mac, Steve Bird, Megan N. C. Grainger y Gregory M. Jacobson. "Low copper levels measured in the aortic wall of New Zealand patients with nonsyndromic ascending thoracic aortic aneurysm". Interactive CardioVascular and Thoracic Surgery, 5 de septiembre de 2022. http://dx.doi.org/10.1093/icvts/ivac235.
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Abstract OBJECTIVES Studies in animals have shown causal relationships between copper (Cu) deficiency and the development of thoracic aortic aneurysms (TAA) [1, 2]. Copper-deficiency is widespread in New Zealand (NZ) soils; the high soil pH from the use of lime fertilizers reduces the bioavailability of Cu for grazing animals and growing plants; this, in turn, reduces Cu availability in the NZ human food chain. Our study is a pilot study to explore associations between copper and TAA. We measured Cu levels in aneurysmal aortic tissues in patients undergoing Bentall procedures and non-aneurysmal aortic tissue from Coronary Artery Bypass Graft (CABG) patients. METHODS Aortic samples were collected from two groups of patients during elective open-heart surgery over four months between November 2017 and February 2018. The groups were a TAA group, patients with non-syndromic Aortic aneurysm and without the bicuspid aortic valve or known infectious or inflammatory condition (ANEURYSM; n = 13), and a control CABG group (CONTROL; n = 44). Standardized digested dry tissue weighed samples were analyzed from both groups. Tissue extraction of trace elements was carried out using HCl-H2O2 digestion and a highly sensitive analytical technique, Inductively Coupled Plasma Mass Spectrometry (ICP-MS) - used to measure elemental concentrations. RESULTS Copper concentration (mean ± SD) was significantly lower in ANEURYSM (3.34 ± 0.16 ug/g) when compared to the CONTROL group tissues (4.33 ± 0.20 ug/g) (dry weight; mean±SD; Student's t-test p < 0.05). Over 46% of the Aneurysm patients were Maori and live in a geographically copper-deficient NZ territory. CONCLUSIONS Copper deficiency may play a role in the development or progression of non-syndromic ascending aortic aneurysms in NZ. Maori patients are more at risk as they commonly live in rural New Zealand, dependant on locally grown nutritional sources. Further studies are required to confirm this exciting finding and to establish cause and effect relationship.
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Surman, Timothy Luke, John Matthew Abrahams, Jim Manavis, John Finnie, Dermot O’Rourke, Karen Jane Reynolds, James Edwards, Michael George Worthington y John Beltrame. "Histological regional analysis of the aortic root and thoracic ascending aorta: a complete analysis of aneurysms from root to arch". Journal of Cardiothoracic Surgery 16, n.º 1 (8 de septiembre de 2021). http://dx.doi.org/10.1186/s13019-021-01641-5.
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Abstract Background Although aortic root and ascending aortic aneurysms are treated the same, they differ in embryological development and pathological processes. This study examines the microscopic structural differences between aortic root and ascending aortic aneurysms, correlating these features to the macroscopic pathophysiological processes. Methods We obtained surgical samples from ascending aortic aneurysms (n = 11), aortic root aneurysms (n = 3), and non-aneurysmal patients (n = 7), Aortic collagen and elastin content were examined via histological analysis, and immunohistochemistry techniques used to determine collagen I, III, and IV subtypes. Analysis was via observational features, and colour deconvolution quantification techniques. Results Elastin fiber disruption and fragmentation was the most extensive in the proximal aneurysmal regions. Medial fibrosis and collagen density increased in proximal aneurysmal regions and aortic root aneurysms (p < 0.005). Collagen I was seen in highest quantity in aortic root aneurysms. Collagen I content was greatest in the sinus tissue regions compared to the valvular and ostial regions (p < 0.005) Collagen III and IV quantification did not vary greatly. The most susceptible regions to ultrastructural changes in disease are the proximal ascending aorta and aortic root. Conclusions The aortic root differs histologically from the ascending aorta confirming its unique composition in aneurysm pathology. These findings should prompt further evaluation on the influence of this altered structure on function which could potentially guide clinical management.
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Papakonstantinou, Nikolaos A. y Filippos-Paschalis Rorris. "Elective replacement of the ascending aorta: is the 5.5-cm threshold appropriate? The insidious, small aorta". European Journal of Cardio-Thoracic Surgery, 23 de noviembre de 2020. http://dx.doi.org/10.1093/ejcts/ezaa387.
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Summary OBJECTIVES As thoracic aortic aneurysm disease continues to cause significant morbidity and mortality in the general population, the cardiovascular community continues the search for the golden threshold of elective surgical replacement of the ascending aorta. METHODS Thoracic aortic aneurysm is a common disease, classified within the 20 most common causes of death in patients over 65 years old. Once aortic complications like dissection or rupture occur, they can prove fatal. Prophylactic surgical replacement of the ascending aorta remains the mainstay of treatment to prevent these complications. Current American and European guidelines agree that the threshold for the diameter for elective replacement of the ascending aorta in non-syndromic, asymptomatic aneurysmal disease is 5.5 cm. Overall, aortic dissection is related to poor prognosis, thus making early intervention paramount. RESULTS There is a critical size above which the risk of dissection or rupture becomes extremely high. However, a significant post-dissection increase in diameter is reported, thus rendering the predissection aortic diameter well below the current threshold for elective surgical replacement of the ascending aorta. Moreover, it is widely reported that the majority of acute aortic dissections would not meet the criteria for prophylactic surgery prior to dissection. Additionally, elective surgical ascending aortic replacement in the current era shows a significantly improved risk-benefit ratio, which justifies a more aggressive approach in the management of aortic aneurysmal disease. CONCLUSIONS As a result, there is a lot of discussion in the literature about the requirement of a leftward shifting of the surgical threshold for elective aortic replacement.
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Grewal, Nimrat, Onur Dolmaci, Evert Jansen, Robert Klautz, Antoine Driessen y Robert E. Poelmann. "Thoracic aortopathy in Marfan syndrome overlaps with mechanisms seen in bicuspid aortic valve disease". Frontiers in Cardiovascular Medicine 10 (9 de febrero de 2023). http://dx.doi.org/10.3389/fcvm.2023.1018167.
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BackgroundThoracic aortopathy is a serious complication which is more often seen in patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) than in individuals with a tricuspid aortic valve (TAV). The identification of common pathological mechanisms leading to aortic complications in non-syndromic and syndromic diseases would significantly improve the field of personalized medicine.ObjectiveThis study sought to compare thoracic aortopathy between MFS, BAV, and TAV individuals.Materials and methodsBicuspid aortic valve (BAV; n = 36), TAV (n = 23), and MFS (n = 8) patients were included. Ascending aortic wall specimen were studied for general histologic features, apoptosis, markers of cardiovascular ageing, expression of synthetic and contractile vascular smooth muscle cells (VSMC), and fibrillin-1 expression.ResultsThe MFS group showed many similarities with the dilated BAV. Both patient groups showed a thinner intima (p < 0.0005), a lower expression of contractile VSMCs (p < 0.05), more elastic fiber thinning (p < 0.001), lack of inflammation (p < 0.001), and a decreased progerin expression (p < 0.05) as compared to the TAV. Other features of cardiovascular ageing differed between the BAV and MFS. Dilated BAV patients demonstrated less medial degeneration (p < 0.0001), VSMC nuclei loss (p < 0.0001), apoptosis of the vessel wall (p < 0.03), and elastic fiber fragmentation and disorganization (p < 0.001), as compared to the MFS and dilated TAV.ConclusionThis study showed important similarities in the pathogenesis of thoracic aortic aneurysms in BAV and MFS. These common mechanisms can be further investigated to personalize treatment strategies in non-syndromic and syndromic conditions.
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Paloschi, Valentina. "Abstract 259: Aneurysm Development in Patients With a Bicuspid Aortic Valve Is Not Associated With Transforming Growth Factor-β Activation". Arteriosclerosis, Thrombosis, and Vascular Biology 35, suppl_1 (mayo de 2015). http://dx.doi.org/10.1161/atvb.35.suppl_1.259.
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Objective: Patients with bicuspid aortic valve (BAV) have an increased risk of developing ascending aortic aneurysms. Transforming growth factor-β (TGFβ) is a crucial factor of vascular remodeling, the impaired signaling of which can alter the structure and composition of the extracellular matrix. In this study, we analyzed the activity of TGFβ in aneurysmal and non-aneurysmal ascending aorta from BAV patients, using tricuspid aortic valve (TAV) patients as a reference group. Approach and Results: The response to exogenous TGFβ was analyzed with regard to gene expression in primary aortic smooth muscle cells that were isolated from 7 BAV and 5 TAV patients and in valve fibroblasts from 7 BAV and 8 TAV patients. The set of genes that were significantly changed by TGFβ (217 genes) was compared with gene expression profiles of the ascending aorta from BAV and TAV patients (139 arrays). By principle component analysis, based on the 217 genes, gene expression differed significantly in the intima/media region between aneurysmal BAV and TAV aortas, driven by the response in TAV patients. During the development of aneurysm, the levels of phosphorylated SMADs and the availability of free TGFβ were lower in BAV patients compared with TAV patients. Confocal microscopy analysis showed a higher co-localization of latency associated peptide and latent TGF-beta binding protein 3 in BAV aortas. Conclusions: Our findings suggest that TGFβ activation during aneurysm formation is muted in patients with BAV and, by interfering with repair processes, could explain the greater propensity of BAV to aortic complications.
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Balint, Brittany, Jan Federspiel, Catherine Kollmann, Paul Teping, Tanja Schwab y Hans-Joachim Schäfers. "SMAD3 contributes to ascending aortic dilatation independent of transforming growth factor-beta in bicuspid and unicuspid aortic valve disease". Scientific Reports 12, n.º 1 (14 de septiembre de 2022). http://dx.doi.org/10.1038/s41598-022-19335-w.
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AbstractWe sought to determine whether there are differences in transforming growth factor-beta (TGFß) signaling in aneurysms associated with bicuspid (BAV) and unicuspid (UAV) aortic valves versus normal aortic valves. Ascending aortic aneurysms are frequently associated with BAV and UAV. The mechanisms are not yet clearly defined, but similarities to transforming growth factor-beta TGFß vasculopathies (i.e. Marfan, Loeys-Dietz syndromes) are reported. Non-dilated (ND) and aneurysmal (D) ascending aortic tissue was collected intra-operatively from individuals with a TAV (N = 10ND, 10D), BAV (N = 7ND, 8D) or UAV (N = 7ND, 8D). TGFß signaling and aortic remodeling were assessed through immuno-assays and histological analyses. TGFß1 was increased in BAV/UAV-ND aortas versus TAV (P = 0.02 and 0.04, respectively). Interestingly, TGFß1 increased with dilatation in TAV (P = 0.03) and decreased in BAV/UAV (P = 0.001). In TAV, SMAD2 and SMAD3 phosphorylation (pSMAD2, pSMAD3) increased with dilatation (all P = 0.04) and with TGFß1 concentration (P = 0.04 and 0.03). No relationship between TGFß1 and pSMAD2 or pSMAD3 was observed for BAV/UAV (all P > 0.05). pSMAD3 increased with dilatation in BAV/UAV aortas (P = 0.01), whereas no relationship with pSMAD2 was observed (P = 0.56). Elastin breaks increased with dilatation in all groups (all P < 0.05). In TAV, elastin degradation correlated with TGFß1, pSMAD2 and pSMAD3 (all P < 0.05), whereas in BAV and UAV aortas, elastin degradation correlated only with pSMAD3 (P = 0.0007). TGFß signaling through SMAD2/SMAD3 contributes to aortic remodeling in TAV, whereas TGFß-independent activation of SMAD3 may underlie aneurysm formation in BAV/UAV aortas. Therefore, SMAD3 should be further investigated as a therapeutic target against ascending aortic dilatation in general, and particularly in BAV/UAV patients.
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Iliopoulos, Dimitrios C. y Dimitrios P. Sokolis. "Ascending aorta mechanics in bicuspid aortopathy: controversy or fact?" Asian Cardiovascular and Thoracic Annals, 25 de mayo de 2020, 021849232092873. http://dx.doi.org/10.1177/0218492320928731.
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Bicuspid aortic valve is the most common congenital cardiovascular defect, often associated with proximal aortic dilatation, and the ideal management strategy is debated. The inconsistency in previous and present guideline recommendations emphasizes the insufficiency of the maximal diameter as the sole criterion for prophylactic repair. Our ability to guide clinical decisions may improve through an understanding of the mechanical properties of ascending thoracic aortic aneurysms in bicuspid compared to tricuspid aortic valve patients and non-aneurysmal aortas, because dissection and rupture are aortic wall mechanical failures. Such an understanding of the mechanical properties has been attempted by several authors, and this article addresses whether there is a controversy in the accumulated knowledge. The available mechanical studies are briefly reviewed, discussing factors such as age, sex, and the region of mechanical examination that may be responsible for the lack of unanimity in the reported findings. The rationale for acquiring layer-specific properties is presented along with the main results from our recent study. No mechanical vulnerability of ascending thoracic aortic aneurysms was evidenced in bicuspid aortic valve patients, corroborating present conservative guidelines concerning the management of bicuspid aortopathy. Weakening and additional vulnerability was evidenced in aged patients and those with coexisting valve pathology, aortic root dilatation, hypertension, and hyperlipidemia. Discussion of these results from age- and sex-matched subjects, accounting for the region- and layer-specific aortic heterogeneity, in relation to intact wall results and histologic confirmation, helps to reconcile previous findings and affords a universal interpretation of ascending aorta mechanics in bicuspid aortopathy.