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Статті в журналах з теми "Intraplaque neovascularization"

Автор: Grafiati

Опубліковано: 29 березня 2025

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1

Koole, Dave, Jan Heyligers, Frans L. Moll, and Gerard Pasterkamp. "Intraplaque neovascularization and hemorrhage." Journal of Cardiovascular Medicine 13, no. 10 (October 2012): 635–39. http://dx.doi.org/10.2459/jcm.0b013e3283590cd2.

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2

Akkus, Zeynettin, Gerard van Burken, Stijn C. H. van den Oord, Arend F. L. Schinkel, Nico de Jong, Antonius F. W. van der Steen, and Johan G. Bosch. "Carotid Intraplaque Neovascularization Quantification Software (CINQS)." IEEE Journal of Biomedical and Health Informatics 19, no. 1 (January 2015): 332–38. http://dx.doi.org/10.1109/jbhi.2014.2306454.

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3

Evdokimenko, A. N., A. O. Chechetkin, L. D. Druina, and M. M. Tanashyan. "Contrast-enhanced ultrasonography for assessing neovascularization of carotid atherosclerotic plaque." Exosomes, no. 4 (July 31, 2019): 24–31. http://dx.doi.org/10.24075/brsmu.2019.057.

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Анотація:

Neovascularization of a carotid atherosclerotic plaque (AP) is associated with an increased risk of stroke. Contrast-enhanced ultrasonography (CEUS) is a widely used method for imaging intraplaque neovascularization in vivo. Unfortunately, there are no standardized guidelines for CEUS interpretation. The aim of this study was to identify the most reliable method for CEUS-based assessment of AP neovascularization. Seventy-eight AP were removed during carotid endarterectomy in 73 patients, of whom 5 had AP on both sides, and examined morphologically. All patients underwent preoperative duplex scanning and CEUS; Sonovue was used as a contrast agent. AP neovascularization was assessed on a 4-grade visual scale and with 3 different quantitative methods using QLAB software. On the visual scale (method 1), poorly (37%) and moderately (51%) vascularized plaques were the most common. Quantitative analysis (data were presented as Me (Q1; Q3)) revealed that the number of blood vessels per 1 cm2 of the plaque (method 2) was 16 (10; 26), the ratio of the total vessel area to the plaque area (method 3) was 6% (3; 9), and AP ROI (method 4) was 2.6 dB (1.8; 4.1). Significant correlations were demonstrated between the results produced by method 2 and method 3 (р < 0.0001), method 3 and method 2 (p = 0.0006), and between pathomorphological findings and the results produced by methods 1–3, especially method 2 (p < 0.004). AP ROI brightness did not correlate with other results. The presence of hyperechoic components (calcifications) in AP dramatically reduced the reliability of US-based intraplaque neovascularization assessment. The most accurate CEUS-based quantitative method for assessing intraplaque neovascularization is estimation of blood vessel number per 1 cm2 of the plaque.

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4

Ugusman, Azizah, Nur Syahidah Nor Hisam, Nur Syakirah Othman, Nur Najmi Mohamad Anuar, Adila A. Hamid, Jaya Kumar, Maisarah Md Razmi, and Amilia Aminuddin. "Pharmacological interventions for intraplaque neovascularization in atherosclerosis." Pharmacology & Therapeutics 261 (September 2024): 108685. http://dx.doi.org/10.1016/j.pharmthera.2024.108685.

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5

Perrotta, Paola, Bieke Van der Veken, Pieter Van Der Veken, Isabel Pintelon, Laurence Roosens, Elias Adriaenssens, Vincent Timmerman, Pieter-Jan Guns, Guido R. Y. De Meyer, and Wim Martinet. "Partial Inhibition of Glycolysis Reduces Atherogenesis Independent of Intraplaque Neovascularization in Mice." Arteriosclerosis, Thrombosis, and Vascular Biology 40, no. 5 (May 2020): 1168–81. http://dx.doi.org/10.1161/atvbaha.119.313692.

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Objective: Intraplaque neovascularization is an important feature of unstable human atherosclerotic plaques. However, its impact on plaque formation and stability is poorly studied. Because proliferating endothelial cells generate up to 85% of their ATP from glycolysis, we investigated whether pharmacological inhibition of glycolytic flux by the small-molecule 3PO (3-[3-pyridinyl]-1-[4-pyridinyl]-2-propen-1-one) could have beneficial effects on plaque formation and composition. Approach and Results: ApoE −/ − (apolipoprotein E deficient) mice treated with 3PO (50 µg/g, ip; 4×/wk, 4 weeks) showed a metabolic switch toward ketone body formation. Treatment of ApoE −/− Fbn1 C1039G+/− mice with 3PO (50 µg/g, ip) either after 4 (preventive, twice/wk, 10 weeks) or 16 weeks of Western diet (curative, 4×/wk, 4 weeks) inhibited intraplaque neovascularization by 50% and 38%, respectively. Plaque formation was significantly reduced in all 3PO-treated animals. This effect was independent of intraplaque neovascularization. In vitro experiments showed that 3PO favors an anti-inflammatory M2 macrophage subtype and suppresses an M1 proinflammatory phenotype. Moreover, 3PO induced autophagy, which in turn impaired NF-κB (nuclear factor-kappa B) signaling and inhibited TNF-α (tumor necrosis factor-alpha)–mediated VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) upregulation. Consistently, a preventive 3PO regimen reduced endothelial VCAM-1 expression in vivo. Furthermore, 3PO improved cardiac function in ApoE −/− Fbn1 C1039G+/− mice after 10 weeks of treatment. Conclusions: Partial inhibition of glycolysis restrained intraplaque angiogenesis without affecting plaque composition. However, less plaques were formed, which was accompanied by downregulation of endothelial adhesion molecules—an event that depends on autophagy induction. Inhibition of coronary plaque formation by 3PO resulted in an overall improved cardiac function.

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6

Filis, Konstantinos, Levon Toufektzian, George Galyfos, Fragiska Sigala, Panagiota Kourkoveli, Sotirios Georgopoulos, Manolis Vavuranakis, Dimitrios Vrachatis, and George Zografos. "Assessment of the vulnerable carotid atherosclerotic plaque using contrast-enhanced ultrasonography." Vascular 25, no. 3 (August 31, 2016): 316–25. http://dx.doi.org/10.1177/1708538116665734.

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Анотація:

Carotid atherosclerosis represents a primary cause for cerebrovascular ischemic events and its contemporary management includes surgical revascularization for moderate to severe symptomatic stenoses. However, the role of invasive therapy seems to be questioned lately for asymptomatic cases. Numerous reports have suggested that the presence of neovessels within the atherosclerotic plaque remains a significant vulnerability factor and over the last decade imaging modalities have been used to identify intraplaque neovascularization in an attempt to risk-stratify patients and offer management guidance. Contrast-enhanced ultrasonography of the carotid artery is a relatively novel diagnostic tool that exploits resonated ultrasound waves from circulating microbubbles. This property permits vascular visualization by producing superior angiography-like images, and allows the identification of vasa vasorum and intraplaque microvessels. Moreover, plaque neovascularization has been associated with plaque vulnerability and ischemic symptoms lately as well. At the same time, attempts have been made to quantify contrast-enhanced ultrasonography signal using sophisticated software packages and algorithms, and to correlate it with intraplaque microvascular density. The aim of this review was to collect all recent data on the characteristics, performance, and prognostic role of contrast-enhanced ultrasonography regarding carotid stenosis management, and to produce useful conclusions for clinical practice.

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7

Schinkel, Arend F. L., Johan G. Bosch, Daniel Staub, Dan Adam, and Steven B. Feinstein. "Contrast-Enhanced Ultrasound to Assess Carotid Intraplaque Neovascularization." Ultrasound in Medicine & Biology 46, no. 3 (March 2020): 466–78. http://dx.doi.org/10.1016/j.ultrasmedbio.2019.10.020.

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8

Ichibori, Yasuhiro, Daisaku Nakatani, Yasushi Sakata, Kouichi Tachibana, Takashi Akasaka, Shunsuke Saito, Norihide Fukushima, Yoshiki Sawa, Shinsuke Nanto, and Issei Komuro. "Cardiac Allograft Vasculopathy Progression Associated With Intraplaque Neovascularization." Journal of the American College of Cardiology 61, no. 9 (March 2013): e149. http://dx.doi.org/10.1016/j.jacc.2012.08.1036.

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9

Kashiwazaki, Daina, Masaki Koh, Haruto Uchino, Naoki Akioka, Naoya Kuwayama, Kyo Noguchi, and Satoshi Kuroda. "Hypoxia accelerates intraplaque neovascularization derived from endothelial progenitor cells in carotid stenosis." Journal of Neurosurgery 131, no. 3 (September 2019): 884–91. http://dx.doi.org/10.3171/2018.4.jns172876.

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OBJECTIVEThe relationship between intraplaque hypoxia and intraplaque hemorrhage (IPH) has been reported, but the details remain obscure. In this study, the authors aimed to clarify the relationship among intraplaque hypoxia, endothelial progenitor cells (EPCs), and neovascularization, which causes IPH. The histological findings of specimens obtained from carotid endarterectomy were assessed.METHODSThis study included 49 patients who underwent carotid endarterectomy. Magnetic resonance plaque imaging was performed to analyze the components of the carotid plaques, and surgical specimens were subjected to immunohistochemical analysis. The numbers of hypoxia-inducible factor-1 alpha (HIF-1α)–, CD34-, CD133-, and vascular endothelial growth factor receptor-2 (VEGFR-2)–positive cells in the carotid plaques were precisely quantified, as were the number and maximum diameter of CD31-positive microvessels.RESULTSPlaque components were judged as fibrous in 7 samples, lipid-rich in 22, and IPH in 20. The number of CD34-, VEGFR-2–, and CD133-positive cells as an EPC-specific marker was significantly correlated with the number of HIF-1α–positive cells (r = 0.9, r = 0.82, and r = 0.81, respectively). These numbers varied among the 3 plaque components (IPH > lipid-rich > fibrous). The number and maximum luminal diameter of CD31-positive microvessels were also significantly correlated with the number of HIF-1α–positive cells (r = 0.85 and r = 0.89, respectively) and varied among the 3 plaque components (IPH > lipid-rich > fibrous).CONCLUSIONSThe present findings suggest that intraplaque hypoxia may accelerate abnormal microvessel formation derived from EPCs, which in turn promotes IPH. The results also suggest that microvessel enlargement is a pivotal characteristic of IPH and these enlarged microvessels are immature endothelial tubes with disorganized branching and are fragile and prone to rupture.

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10

Koganti, S., A. Karanasos, S. Tu, R. D. Rakhit, and E. Regar. "Visualization of extensive intraplaque neovascularization by optical coherence tomography." Hellenic Journal of Cardiology 58, no. 1 (January 2017): 87–88. http://dx.doi.org/10.1016/j.hjc.2017.01.011.

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11

Perrotta, Paola, Isabel Pintelon, Margreet R. de Vries, Paul H. A. Quax, Jean-Pierre Timmermans, Guido R. Y. De Meyer, and Wim Martinet. "Three-Dimensional Imaging of Intraplaque Neovascularization in a Mouse Model of Advanced Atherosclerosis." Journal of Vascular Research 57, no. 6 (2020): 348–54. http://dx.doi.org/10.1159/000508449.

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Multiple lines of evidence suggest that intraplaque (IP) neovascularization promotes atherosclerotic plaque growth, destabilization, and rupture. However, pharmacological inhibition of IP neovascularization remains largely unexplored due to the limited number of animal models that develop IP neovessels and the lack of reliable methods for visualizing IP angiogenesis. Here, we applied 3D confocal microscopy with an optimized tissue-clearing process, immunolabeling-enabled three-dimensional imaging of solvent-cleared organs, to visualize IP neovessels in apolipoprotein E-deficient (ApoE<sup>−/−</sup>) mice carrying a heterozygous mutation (C1039+/−) in the fibrillin-1 gene. Unlike regular ApoE<sup>−/−</sup> mice, this mouse model is characterized by the presence of advanced plaques with evident IP neovascularization. Plaques were stained with antibodies against endothelial marker CD31 for 3 days, followed by incubation with fluorescently labeled secondary antibodies. Subsequent tissue clearing with dichloromethane (DCM)/methanol, DCM, and dibenzyl ether allowed easy visualization and 3D reconstruction of the IP vascular network while plaque morphology remained intact.

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12

Mantella, Laura E., Kayla N. Colledanchise, Marie-France Hétu, Steven B. Feinstein, Joseph Abunassar, and Amer M. Johri. "Carotid intraplaque neovascularization predicts coronary artery disease and cardiovascular events." European Heart Journal - Cardiovascular Imaging 20, no. 11 (April 12, 2019): 1239–47. http://dx.doi.org/10.1093/ehjci/jez070.

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Abstract Aims It is thought that the majority of cardiovascular (CV) events are caused by vulnerable plaque. Such lesions are rupture prone, in part due to neovascularization. It is postulated that plaque vulnerability may be a systemic process and that vulnerable lesions may co-exist at multiple sites in the vascular bed. This study sought to examine whether carotid plaque vulnerability, characterized by contrast-enhanced ultrasound (CEUS)-assessed intraplaque neovascularization (IPN), was associated with significant coronary artery disease (CAD) and future CV events. Methods and results We investigated carotid IPN using carotid CEUS in 459 consecutive stable patients referred for coronary angiography. IPN was graded based on the presence and location of microbubbles within each plaque (0, not visible; 1, peri-adventitial; and 2, plaque core). The grades of each plaque were averaged to obtain an overall score per patient. Coronary plaque severity and complexity was also determined angiographically. Patients were followed for 30 days following their angiogram. This study found that a higher CEUS-assessed carotid IPN score was associated with significant CAD (≥50% stenosis) (1.8 ± 0.4 vs. 0.5 ± 0.6, P < 0.0001) and greater complexity of coronary lesions (1.7 ± 0.5 vs. 1.3 ± 0.8, P < 0.0001). Furthermore, an IPN score ≥1.25 could predict significant CAD with a high sensitivity (92%) and specificity (89%). The Kaplan–Meier analysis demonstrated a significantly higher proportion of participants having CV events with an IPN score ≥1.25 (P = 0.004). Conclusion Carotid plaque neovascularization was found to be predictive of significant and complex CAD and future CV events. CEUS-assessed carotid IPN is a clinically useful tool for CV risk stratification in high-risk cardiac patients.

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13

Ogata, Atsushi, Tomihiro Wakamiya, Masashi Nishihara, Tatsuya Tanaka, Taichiro Mizokami, Jun Masuoka, Nobuaki Momozaki, Shuji Sakata, Hiroyuki Irie, and Tatsuya Abe. "Association between Pericytes in Intraplaque Neovessels and Magnetic Resonance Angiography Findings." International Journal of Molecular Sciences 21, no. 6 (March 13, 2020): 1980. http://dx.doi.org/10.3390/ijms21061980.

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(1) Background: Pericytes are involved in intraplaque neovascularization of advanced and complicated atherosclerotic lesions. However, the role of pericytes in human carotid plaques is unclear. An unstable carotid plaque that shows high-intensity signals on time-of-flight (TOF) magnetic resonance angiography (MRA) is often a cause of ischemic stroke. The aim of the present study is to examine the relationship between the pericytes in intraplaque neovessels and MRA findings. (2) Methods: A total of 46 patients with 49 carotid artery stenoses who underwent carotid endarterectomy at our hospitals were enrolled. The patients with carotid plaques that were histopathologically evaluated were retrospectively analyzed. Intraplaque hemorrhage was evaluated using glycophorin A staining, and intraplaque neovessels were evaluated using CD34 (Cluster of differentiation) stain as an endothelial cell marker or NG2 (Neuron-glial antigen 2) and CD146 stains as pericyte markers. Additionally, the relationships between the TOF-MRA findings and the carotid plaque pathologies were evaluated. (3) Results: Of the 49 stenoses, 28 had high-intensity signals (TOF-HIS group) and 21 had iso-intensity signals (TOF-IIS group) on TOF-MRA. The density of the CD34-positive neovessels was equivalent in both groups. However, the NG2- and CD146-positive neovessels had significantly higher densities in the TOF-HIS group than in the TOF-IIS group. (4) Conclusion: The presence of a high-intensity signal on TOF-MRA in carotid plaques was associated with intraplaque hemorrhage and few pericytes in intraplaque neovessels. These findings may contribute to the development of new therapeutic strategies focusing on pericytes.

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14

Van der Veken, Bieke, Guido RY De Meyer, and Wim Martinet. "Intraplaque neovascularization as a novel therapeutic target in advanced atherosclerosis." Expert Opinion on Therapeutic Targets 20, no. 10 (May 25, 2016): 1247–57. http://dx.doi.org/10.1080/14728222.2016.1186650.

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15

Tian, JinWei, Jingbo Hou, Lei Xing, Haibo Jia, Shaosong Zhang, Bo Yu, and Ik-Kyung Jang. "SIGNIFICANCE OF INTRAPLAQUE NEOVASCULARIZATION FOR VULNERABILITY: OPTICAL COHERENCE TOMOGRAPHY STUDY." Journal of the American College of Cardiology 59, no. 13 (March 2012): E1439. http://dx.doi.org/10.1016/s0735-1097(12)61440-5.

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16

Coli, Stefano, Marco Magnoni, Giuseppe Sangiorgi, Massimiliano M. Marrocco-Trischitta, Giulio Melisurgo, Alessandro Mauriello, Luigi Spagnoli, Roberto Chiesa, Domenico Cianflone, and Attilio Maseri. "Contrast-Enhanced Ultrasound Imaging of Intraplaque Neovascularization in Carotid Arteries." Journal of the American College of Cardiology 52, no. 3 (July 2008): 223–30. http://dx.doi.org/10.1016/j.jacc.2008.02.082.

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17

Alonso, Angelika, Dimitrios Artemis, and Michael G. Hennerici. "Molecular Imaging of Carotid Plaque Vulnerability." Cerebrovascular Diseases 39, no. 1 (December 24, 2014): 5–12. http://dx.doi.org/10.1159/000369123.

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Background: Carotid endarterectomy (CEA) has been shown to be beneficial in patients with high-grade symptomatic carotid artery stenosis. Patients with high-grade asymptomatic stenosis may only exceptionally benefit from CEA during periods of increased plaque vulnerability. Imaging modalities to characterize unstable, vulnerable plaques are strongly needed for better risk stratification in these patients. Summary: Contrast-enhanced ultrasound (CEUS) is a novel and noninvasive technique capable to identify several surrogate markers of vulnerable carotid plaques. The use of specific ultrasound microbubbles allows a reliable detection of microulcerations due to an optimized visualization of the plaque-lumen border. As microbubbles are strictly intravascular tracers, the detection of individual microbubbles within the plaque corresponds to intraplaque neovessels. The accuracy of CEUS in the visualization of newly formed microvessels has been confirmed in histological studies on carotid endarterectomy specimens. Together with the formation of adventitial vasa vasorum, intraplaque neovascularization is a strong predictor for symptomatic disease. The phenomenon of late phase contrast enhancement is based on the adherence of microbubble-containing monocytes on inflamed endothelium. Recent studies suggest that late phase contrast enhancement may reflect endothelial inflammation or activation within carotid plaques. The development of conjugated microbubbles that bind to specific ligands such as thrombotic material or neovessels has led to the term ‘molecular imaging'. CEUS with microbubbles targeted to P-selectin and VCAM-1, key molecules in leukocyte trafficking, was used to detect an inflammatory plaque phenotype, whereas microbubbles coupled to the VEGF-receptor may allow for a detection of neovascularization. Even though imaging with targeted microbubbles is yet in an experimental stage, this technique can visualize active plaque reorganization with increased vulnerability leading to generation of arterio-arterial embolism. Key Messages: The use of contrast-enhanced ultrasound can be recommended to assess atherosclerotic carotid lesions at risk for rupture. Prospective clinical studies are needed to validate the use of CEUS in patients with high risks of recurrent large artery strokes. In particular, this applies to the detection of intraplaque neovascularization, a well-established marker in preclinical and observational studies, while the clinical significance of late phase contrast enhancement still needs to be determined.

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18

Gerasimova, E., T. Popkova, O. Pogorelova, O. Fomicheva, I. Kirillova, and T. Balakhonova. "POS0520 ASSOCIATIONS BETWEEN THE NEOVASCULARIZATION OF CAROTID ATHEROSCLEROTIC PLAQUES, LIPID PARAMETERS AND IMMUNOLOGICAL DISORDERS IN PATIENTS WITH RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 493.3–493. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1509.

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Background:Development of carotid atherosclerotic plaques (CAP) in patients (pts) with rheumatoid arthritis (RA) is associated with accumulation of traditional risk factors and immunological disorders. CAP neovascularization is associated with its’ inflammation and increasing vulnerability. Therefore, early detection of CAP neovascularization is important for prevention of potential cardiovascular complications, preferably using a non-invasive technique, such as contrast-enhanced ultrasound (CEUS) of the carotid arteries.Objectives:to identify the relationship between the severity of CAP neovascularization, lipid parameters and RA-related parameters.Methods:Evaluation of 23 RA pts, 8 males and 15 females, mean age 61 [58; 65] years, with a longstanding disease (7 [3;12] years), seropositivity for IgM rheumatoid factor (RF) (76%) and anti-cyclic citrullinated peptide (ACCP) (62%) and moderate clinical disease activity (DAS 28 3,9 [3,2;4,8]). Nineteen RA pts (83%) received Methotrexate, 35% - biological agents, 35% - low-dose glucocorticoids. All patients underwent bilateral CEUS of the carotid arteries using a PHILIPS IU22 ultrasound system with 3-9 MHz linear array transducer and i/v administration of SonoVue contrast agent. The severity of carotid intraplaque neovascularization (IPN) was visually assessed on a scale from 0 to 3 (Shah et al. 2007): 0 - no neovascularization, 1 (mild) - limited to moderate neovascularization, 2 (severe) - extensive appearance of neovascularization, 3 - in the presence of a pulsating vessel in the plaque image.Results:Carotid IPN was found in all RA pts. Grade 1 of neovascularization was established in 39% pts (group I) and Grade 2 - in 61% pts (group II). Groups were comparable in terms of age, sex, body mass index, smoking, disease duration and activity RA (DAS 28 score). The degree of carotid IPN positively correlated with the LDL-C level (R = 0,46, p=0,04), and the TG level (R=0,56, p=0,01) and negatively correlated with the HDL-C level (R= -0,52, p=0,02) in all pts. The degree of neovascularization was also associated with RA duration (R=0,52, p<0,05) and ACCP-positivity (R=0,57, p=0,007). Aforementioned correlations were significant for both groups of RA pts. No association was found between the severity of IPN and the levels of RF, DAS28. Association between the degree of carotid stenosis and CRP concentrations (R=-0,73, p<0,05) was found in pts of group II.Conclusion:CEUS of carotid arteries demonstrated the presence of a predominantly extensive carotid IPN in RA pts. Cases of more severe carotid IPN were associated with lipid parameters (positively with the LDL-C, TG levels and negatively with the HDL-C level), RA duration and ACCP-positivity. The relationship between the degree of carotid artery stenosis and CRP requires additional studies to determine the role of immunological disorders in the development of carotid intraplaque neovascularization in RA pts.References:[1]Shah F., Balan P., Weinberg M., Reddy V., Neems R., Feinstein M., Dainauskas J., Meyer P., Goldin M., Feinstein S.B. Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? Vasc Med. 2007;12(4):291-7. https://doi.org/10.1177/1358863x07083363Disclosure of Interests:None declared

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19

Chang, Xiaoni, Jun Feng, Litao Ruan, Jing Shang, Yanqiu Yang, Jian Sun, Ying Dang, and Yan Song. "Positive correlation between neovascularization degree of carotid atherosclerosis determined by contrast-enhanced ultrasound and level of serum C-reactive protein." Vasa 44, no. 3 (May 4, 2015): 0187–94. http://dx.doi.org/10.1024/0301-1526/a000429.

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Background: Neovascularization is one of the most important risk factors for unstable plaque. This study was designed to correlate plaque thickness, artery stenosis and levels of serum C-reactive protein with the degree of intraplaque enhancement determined by contrast-enhanced ultrasound. Patients and methods: Contrast-enhanced ultrasound was performed on 72 carotid atherosclerotic plaques in 48 patients. Contrast enhancement within the plaque was categorized as grade 1, 2 or 3. Maximum plaque thickness was measured in short-axis view. Carotid artery stenosis was categorized as mild, moderate or severe. Results: Plaque contrast enhancement was not associated with the degree of artery stenosis or with plaque thickness. Serum C-reactive protein levels were positively correlated with the number of new vessels in the plaque. C-reactive protein levels increased in the three groups(Grade 1: 3.72±1.79mg/L; Grade 2: 7.88±4.24 mg/L; Grade 3: 11.02±3.52 mg/L), with significant differences among them (F=10.14, P<0.01), and significant differences between each two groups (P<0.05). Spearmans rank correlation analysis showed that serum C-reactive protein levels were positively correlated with the degree of carotid plaque enhancement (Rs =0.69, P<0.01). Conclusions: The combination of C-reactive protein levels and intraplaque neovascularization detected by contrast-enhanced ultrasound may allow more accurate evaluation of plaque stability.

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20

Погорелова, О. А., О. А. Фомичева, М. И. Трипотень, Л. Б. Круглый, Е. В. Герасимова, Ф. Ф. Шингареева, Г. И. Хеймец, Ю. А. Карпов, Т. В. Попкова, and Т. В. Балахонова. "Feasibility of contrast-enhanced ultrasonography for atherosclerotic plaques in carotid arteries in patients with rheumatoid arthritis." Kardiologicheskii vestnik, no. 4 (December 11, 2020): 57–65. http://dx.doi.org/10.36396/ms.2020.15.4.008.

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Введение. Ревматоидный артрит (РА) ассоциируется с повышенным риском сердечно-сосудистых заболеваний по сравнению с общей популя- цией. Для понимания роли системного воспаления в развитии сердечно-сосудистых катастроф у больных РА принципиальное значение имеет концепция о сходстве патогенетических механизмов аутоиммунного воспаления и атеросклероза. Ультразвуковое исследование с контраст- ным усилением (КУУЗИ) позволяет выявить неоваскуляризацию (НВ) атеросклеротической бляшки (АСБ), что отражает воспаление в бляшке и свидетельствует о ее нестабильности. Материал и методы. Был обследован 21 пациент с РА (7 мужчин и 14 женщин) в возрасте 61 (58; 65) год, длительность заболевания 7 (3; 16) лет. КУУЗИ сонных артерий (СА) проводили на ультразвуковой системе Philips IU22 c линейным датчиком 3–9 МГц, с внутривенным введением контрастного препарата «Соновью». Степень НВ бляшки оценивали как 0 — отсутствие НВ, 1 — слабая НВ, 2 — выраженная НВ, 3 — НВ при наличии пульсирующего сосуда. Результаты. У всех больных РА была выявлена НВ бляшки сонной артерии, при этом слабая степень НВ была выявлена в 7 случаях (33,3%), выраженная степень НВ — в 14 (66,7%). При проведении корреляционного анализа по Спирмену выявлена прямая уме- ренная корреляция между степенью НВ и холестерином липопротеидами низкой плотности (ХС ЛПНП) (R = 0,46, р = 0,04), прямая заметная корреляция между степенью НВ и триглицеридами (R = 0,56, р = 0,01), обратная заметная корреляция между степенью НВ и холестерином липопротеидами высокой плотности (R = -0,52, р = 0,02), умеренная корреляция между НВ бляшки и длительностью РА (R = 0,43, р = 0,052), заметная корреляция между НВ и наличием специфических антител к циклическому цитруллинированному пептиду (R = 0,57, р = 0,0068). Не было выявлено взаимосвязи между степенью НВ и уровнем высокочувствительного С-реактив- ного белка, скоростью оседания эритроцитов, холестерина, индексом активности РА DAS28 и наличием специфических антител ревматоидного фактора IgM. Заключение. КУУЗИ продемонстрировало наличие преимущественно высокой степени неоваскуляризации АСБ СА у пациентов с РА. КУУЗИ СА является доступным методом выявления нестабильности атеросклеротической бляшки СА у пациентов с РА с целью ранней профилактики и предотвращения сердечно-сосудистых осложнений Introduction. Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease compared to the general population. Similarity of the pathogenetic mechanisms of autoimmune inflammation and atherosclerosis is fundamentally important for understanding the role of systemic inflammation in the development of cardiovascular complications in RA. Contrast-enhanced ultrasound (CEUS) reveals neovascularization of an atherosclerotic plaque, which reflects inflammation in the plaque and indicates its vulnerability. Material and methods. We examined 21 patients with RA (7 males) with the median age of 61 [58; 65] years old and the median RA duration of 7[3; 16] years. CEUS of the carotid arteries was performed with the PHILIPS IU22 ultrasound system and 3-9 MHz linear array transducer. Ultrasound contrast agent SonoVue was administered intravenously. The degree of carotid intraplaque neovascularization was visually assessed on a scale from 0 to 3. Grade 0 represented no visible neovascularization, grade 1 — limited to moderate neovascularization, grade 2 extensive appearance of neovascularization, grade 3 — presence of a pulsating arterial vessel within the plaque (Shah et al. 2007). The association between the degree of neovascularization, biochemical parameters and RA duration was assessed with the Spearman’s correlation coefficient. Results. All patients with RA were found to have carotid intraplaque neovascularization. Grade 1 of neovascularization was detected in 33.3 % of patients and grade 2 was detected in 66.7%. The degree of neovascularization was positively associated with the LDL-C level (R = 0,46, p = 0,04), and the TG level (R = 0,56, p = 0,01) and negatively associated with the HDL-C level (R = -0,52, p = 0,02). The degree of neovascularization was also associated with RA duration (R = 0,43, p = 0,052) and the presence of antibodies against cyclic citrullinated peptides (aCCP) (R = 0,57, p = 0,0068). No association was found between the degree of neovascularization and the levels of hs-CRP, ESR, cholesterol, the RA activity index DAS28 and the presence of rheumatoid factor (RF). Conclusion. CEUS of carotid arteries demonstrated the presence of a predominantly extensive degree of carotid intraplaque neovascularization in patients with RA. CEUS of the carotid arteries is a readily accessible method for detecting plaque vulnerability and can be used for early detection and prevention of cardiovascular complications in patients with RA

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Погорелова, О. А., О. А. Фомичева, М. И. Трипотень, Л. Б. Круглый, Е. В. Герасимова, Ф. Ф. Шингареева, Г. И. Хеймец, Ю. А. Карпов, Т. В. Попкова, and Т. В. Балахонова. "Feasibility of contrast-enhanced ultrasonography for atherosclerotic plaques in carotid arteries in patients with rheumatoid arthritis." Kardiologicheskii vestnik, no. 4 (December 11, 2020): 57–65. http://dx.doi.org/10.36396/ms.2020.15.4.008.

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Анотація:

Введение. Ревматоидный артрит (РА) ассоциируется с повышенным риском сердечно-сосудистых заболеваний по сравнению с общей популя- цией. Для понимания роли системного воспаления в развитии сердечно-сосудистых катастроф у больных РА принципиальное значение имеет концепция о сходстве патогенетических механизмов аутоиммунного воспаления и атеросклероза. Ультразвуковое исследование с контраст- ным усилением (КУУЗИ) позволяет выявить неоваскуляризацию (НВ) атеросклеротической бляшки (АСБ), что отражает воспаление в бляшке и свидетельствует о ее нестабильности. Материал и методы. Был обследован 21 пациент с РА (7 мужчин и 14 женщин) в возрасте 61 (58; 65) год, длительность заболевания 7 (3; 16) лет. КУУЗИ сонных артерий (СА) проводили на ультразвуковой системе Philips IU22 c линейным датчиком 3–9 МГц, с внутривенным введением контрастного препарата «Соновью». Степень НВ бляшки оценивали как 0 — отсутствие НВ, 1 — слабая НВ, 2 — выраженная НВ, 3 — НВ при наличии пульсирующего сосуда. Результаты. У всех больных РА была выявлена НВ бляшки сонной артерии, при этом слабая степень НВ была выявлена в 7 случаях (33,3%), выраженная степень НВ — в 14 (66,7%). При проведении корреляционного анализа по Спирмену выявлена прямая уме- ренная корреляция между степенью НВ и холестерином липопротеидами низкой плотности (ХС ЛПНП) (R = 0,46, р = 0,04), прямая заметная корреляция между степенью НВ и триглицеридами (R = 0,56, р = 0,01), обратная заметная корреляция между степенью НВ и холестерином липопротеидами высокой плотности (R = -0,52, р = 0,02), умеренная корреляция между НВ бляшки и длительностью РА (R = 0,43, р = 0,052), заметная корреляция между НВ и наличием специфических антител к циклическому цитруллинированному пептиду (R = 0,57, р = 0,0068). Не было выявлено взаимосвязи между степенью НВ и уровнем высокочувствительного С-реактив- ного белка, скоростью оседания эритроцитов, холестерина, индексом активности РА DAS28 и наличием специфических антител ревматоидного фактора IgM. Заключение. КУУЗИ продемонстрировало наличие преимущественно высокой степени неоваскуляризации АСБ СА у пациентов с РА. КУУЗИ СА является доступным методом выявления нестабильности атеросклеротической бляшки СА у пациентов с РА с целью ранней профилактики и предотвращения сердечно-сосудистых осложнений Introduction. Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease compared to the general population. Similarity of the pathogenetic mechanisms of autoimmune inflammation and atherosclerosis is fundamentally important for understanding the role of systemic inflammation in the development of cardiovascular complications in RA. Contrast-enhanced ultrasound (CEUS) reveals neovascularization of an atherosclerotic plaque, which reflects inflammation in the plaque and indicates its vulnerability. Material and methods. We examined 21 patients with RA (7 males) with the median age of 61 [58; 65] years old and the median RA duration of 7[3; 16] years. CEUS of the carotid arteries was performed with the PHILIPS IU22 ultrasound system and 3-9 MHz linear array transducer. Ultrasound contrast agent SonoVue was administered intravenously. The degree of carotid intraplaque neovascularization was visually assessed on a scale from 0 to 3. Grade 0 represented no visible neovascularization, grade 1 — limited to moderate neovascularization, grade 2 extensive appearance of neovascularization, grade 3 — presence of a pulsating arterial vessel within the plaque (Shah et al. 2007). The association between the degree of neovascularization, biochemical parameters and RA duration was assessed with the Spearman’s correlation coefficient. Results. All patients with RA were found to have carotid intraplaque neovascularization. Grade 1 of neovascularization was detected in 33.3 % of patients and grade 2 was detected in 66.7%. The degree of neovascularization was positively associated with the LDL-C level (R = 0,46, p = 0,04), and the TG level (R = 0,56, p = 0,01) and negatively associated with the HDL-C level (R = -0,52, p = 0,02). The degree of neovascularization was also associated with RA duration (R = 0,43, p = 0,052) and the presence of antibodies against cyclic citrullinated peptides (aCCP) (R = 0,57, p = 0,0068). No association was found between the degree of neovascularization and the levels of hs-CRP, ESR, cholesterol, the RA activity index DAS28 and the presence of rheumatoid factor (RF). Conclusion. CEUS of carotid arteries demonstrated the presence of a predominantly extensive degree of carotid intraplaque neovascularization in patients with RA. CEUS of the carotid arteries is a readily accessible method for detecting plaque vulnerability and can be used for early detection and prevention of cardiovascular complications in patients with RA

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22

Song, Yan, Ying Dang, Hao Li, Jun Feng, and Litao Ruan. "Relationship between carotid intraplaque neovascularization and haemoglobin A1c in diabetic patients." Clinical Neurology and Neurosurgery 203 (April 2021): 106515. http://dx.doi.org/10.1016/j.clineuro.2021.106515.

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23

Guo, Muyi, and Yan Cai and Zhiyong Li. "Neovascularization and Intraplaque Hemorrhage in Atherosclerotic Plaque Destabilization-A Mathematical Model." Molecular & Cellular Biomechanics 16, s1 (2019): 49. http://dx.doi.org/10.32604/mcb.2019.05727.

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Finn, Aloke V., Frank D. Kolodgie, Masataka Nakano, and Renu Virmani. "The Differences Between Neovascularization of Chronic Total Occlusion and Intraplaque Angiogenesis." JACC: Cardiovascular Imaging 3, no. 8 (August 2010): 806–10. http://dx.doi.org/10.1016/j.jcmg.2010.03.011.

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25

Bellengier, C., L. Ferri, M. Tardivel, A. Bongiovanni, S. Delhaye, C. Duhem, Q. Thorel та ін. "The role of the nuclear receptor Rev-erbΑ during intraplaque neovascularization". Atherosclerosis 379 (серпень 2023): S23. http://dx.doi.org/10.1016/j.atherosclerosis.2023.06.747.

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26

Balmos, Ioan Alexandru, Mark Slevin, Klara Brinzaniuc, Adrian Vasile Muresan, Horatiu Suciu, Gyopár Beáta Molnár, Adriana Mocian, Béla Szabó, Előd Ernő Nagy, and Emőke Horváth. "Intraplaque Neovascularization, CD68+ and iNOS2+ Macrophage Infiltrate Intensity Are Associated with Atherothrombosis and Intraplaque Hemorrhage in Severe Carotid Atherosclerosis." Biomedicines 11, no. 12 (December 11, 2023): 3275. http://dx.doi.org/10.3390/biomedicines11123275.

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Background: Atherosclerosis is a progressive disease that results from endothelial dysfunction, inflammatory arterial wall disorder and the formation of the atheromatous plaque. This results in carotid artery stenosis and is responsible for atherothrombotic stroke and ischemic injury. Low-grade plaque inflammation determines biological stability and lesion progression. Methods: Sixty-seven cases with active perilesional inflammatory cell infiltrate were selected from a larger cohort of patients undergoing carotid endarterectomy. CD68+, iNOS2+ and Arg1+ macrophages and CD31+ endothelial cells were quantified around the atheroma lipid core using digital morphometry, and expression levels were correlated with determinants of instability: ulceration, thrombosis, plaque hemorrhage, calcification patterns and neovessel formation. Results: Patients with intraplaque hemorrhage had greater CD68+ macrophage infiltration (p = 0.003). In 12 cases where iNOS2 predominated over Arg1 positivity, the occurrence of atherothrombotic events was significantly more frequent (p = 0.046). CD31 expression, representing neovessel formation, correlated positively with atherothrombosis (p = 0.020). Conclusions: Intraplaque hemorrhage is often described against the background of an intense inflammatory cell infiltrate. Atherothrombosis is associated with the presence of neovessels and pro-inflammatory macrophages expressing iNOS2. Modulating macrophage polarization may be a successful therapeutic approach to prevent plaque destabilization.

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Song, Yan, Ying Dang, Jichang Wang, Hui Cai, Jun Feng, Hongmei Zhang, and Litao Ruan. "Carotid Intraplaque Neovascularization Predicts Ischemic Stroke Recurrence in Patients with Carotid Atherosclerosis." Gerontology 67, no. 2 (2021): 144–51. http://dx.doi.org/10.1159/000511360.

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<b><i>Introduction:</i></b> This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke recurrence in patients with carotid atherosclerosis. <b><i>Methods:</i></b> We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the carotid artery on the side consistent with symptoms. All patients underwent CEUS after their first admission. IPN was graded on the basis of the presence and location of microbubbles within each plaque. <b><i>Results:</i></b> We eventually included 155 patients, all of whom underwent IPN analysis. After a follow-up of 24 months, we recorded 25 (16.1%) stroke recurrences in the whole population. All the recurrences occurred in patients presenting IPN. There was significant difference in the IPN between the 2 groups (<i>p</i> = 0.002). In the final Cox proportional-hazards multivariable models, IPN of grade 2 was independently associated with the risk of stroke recurrence (HR = 4.535; 95% CI: 1.892–10.870; <i>p</i> = 0.001). This association remained after adjusting for the degree of carotid stenosis (HR = 3.491; 95% CI: 1.410–8.646; <i>p</i> = 0.007). <b><i>Conclusions:</i></b> IPN was an independent predictor of stroke recurrence in patients with a recent ischemic stroke and carotid atherosclerosis. In predicting stroke recurrence, IPN may be an earlier indicator than carotid stenosis and may help stratify the risk of stroke recurrence.

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Li, Zhuo, Zhen Qin, Xiangyi Kong, Baiqiang Chen, Wenjie Hu, Zhiqi Lin, Yugong Feng, Huanting Li, Qi Wan, and Shifang Li. "CCL14 exacerbates intraplaque vulnerability by promoting neovascularization in the human carotid plaque." Journal of Stroke and Cerebrovascular Diseases 31, no. 10 (October 2022): 106670. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2022.106670.

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Chistiakov, D. A., A. N. Orekhov, and Y. V. Bobryshev. "Contribution of neovascularization and intraplaque haemorrhage to atherosclerotic plaque progression and instability." Acta Physiologica 213, no. 3 (January 2, 2015): 539–53. http://dx.doi.org/10.1111/apha.12438.

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Oura, Kazumasa, Tadayoshi Kato, Hideki Ohba, and Yasuo Terayama. "Evaluation of Intraplaque Neovascularization Using Superb Microvascular Imaging and Contrast-Enhanced Ultrasonography." Journal of Stroke and Cerebrovascular Diseases 27, no. 9 (September 2018): 2348–53. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.04.023.

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Guo, Muyi, Yan Cai, Xinke Yao, and Zhiyong Li. "Mathematical modeling of atherosclerotic plaque destabilization: Role of neovascularization and intraplaque hemorrhage." Journal of Theoretical Biology 450 (August 2018): 53–65. http://dx.doi.org/10.1016/j.jtbi.2018.04.031.

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van den Oord, S., Z. Akkus, J. Bosch, A. Hoogi, G. ten Kate, G. Renaud, E. Sijbrands, et al. "Quantitative Contrast-Enhanced Ultrasound of Intraplaque Neovascularization in Patients with Carotid Atherosclerosis." Ultraschall in der Medizin - European Journal of Ultrasound 36, no. 02 (May 13, 2014): 154–61. http://dx.doi.org/10.1055/s-0034-1366410.

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Ning, Bin, Dong Zhang, Wen He, Li Shu Wang, and Zhan Qiang Jin. "A Study on Distribution Features of Neovascularization in Atherosclerotic Carotid Artery Plaques: Comparing Contrast-enhanced Ultrasound with Histopathology." Ultrasonic Imaging 41, no. 2 (February 1, 2019): 115–25. http://dx.doi.org/10.1177/0161734618824941.

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Intraplaque neovascularization (IPNV) is a characteristic feature of the vulnerable plaques. In this study of neovessels of carotid plaques, we assessed intraplaque echogenicity and plaque surface morphology, and performed contrast-enhanced ultrasound (CEUS) to observe the location and grading of neovessels to identify the vulnerability of plaques. The results showed that plaque with a ruptured fibrous cap on the histopathological images presented as a sunken or fissured surface on corresponding ultrasound images. Both in the symptomatic and asymptomatic groups, plaque echogenicity did not correlate with neovessels grading. The neovessels that appeared in the tunica media and base of the plaque in the symptomatic and asymptomatic group on CEUS had no statistical difference ( p > 0.05), but those located in the fibrous cap and shoulders had a significant statistical difference ( p = 0.000). Statistical differences were not found in the locations of IPNV on CEUS and histopathology (all p > 0.05). The sensitivity (82.4%, 56/68) and specificity (77.4%, 24/31) of IPNV location were higher than those (77.9%, 53/68; 45.2%, 14/31) of IPNV grading in the identification of plaque vulnerability. IPNVs located at the fibrous cap and shoulders on CEUS is a reliable indicator for identifying plaque vulnerability.

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Kopyto, Ewa, Marcin Czeczelewski, Eryk Mikos, Karol Stępniak, Maja Kopyto, Małgorzata Matuszek, Karolina Nieoczym, et al. "Contrast-Enhanced Ultrasound Feasibility in Assessing Carotid Plaque Vulnerability—Narrative Review." Journal of Clinical Medicine 12, no. 19 (October 9, 2023): 6416. http://dx.doi.org/10.3390/jcm12196416.

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The risk assessment for carotid atherosclerotic lesions involves not only determining the degree of stenosis but also plaque morphology and its composition. Recently, carotid contrast-enhanced ultrasound (CEUS) has gained importance for evaluating vulnerable plaques. This review explores CEUS’s utility in detecting carotid plaque surface irregularities and ulcerations as well as intraplaque neovascularization and its alignment with histology. Initial indications suggest that CEUS might have the potential to anticipate cerebrovascular incidents. Nevertheless, there is a need for extensive, multicenter prospective studies that explore the relationships between CEUS observations and patient clinical outcomes in cases of carotid atherosclerotic disease.

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Chistiakov, Dimitry A., Alexandra A. Melnichenko, Veronika A. Myasoedova, Andrey V. Grechko, and Alexander N. Orekhov. "Role of lipids and intraplaque hypoxia in the formation of neovascularization in atherosclerosis." Annals of Medicine 49, no. 8 (August 22, 2017): 661–77. http://dx.doi.org/10.1080/07853890.2017.1366041.

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Giannarelli, Chiara, Borja Ibanez, Giovanni Cimmino, Josè M. Garcia Ruiz, Francesco Faita, Elisabetta Bianchini, M. Urooj Zafar, Valentin Fuster, Mario J. Garcia, and Juan J. Badimon. "Contrast-Enhanced Ultrasound Imaging Detects Intraplaque Neovascularization in an Experimental Model of Atherosclerosis." JACC: Cardiovascular Imaging 3, no. 12 (December 2010): 1256–64. http://dx.doi.org/10.1016/j.jcmg.2010.09.017.

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37

Cui, Edward, Georgia Kersche, Nicholas Grubic, Marie-France Hetu, Stephen Pang, and Amer Johri. "EFFECT OF PHARMACOLOGIC ANTI-ATHEROSCLEROTIC THERAPY ON CAROTID INTRAPLAQUE NEOVASCULARIZATION: A SYSTEMATIC REVIEW." Journal of the American College of Cardiology 81, no. 8 (March 2023): 1460. http://dx.doi.org/10.1016/s0735-1097(23)01904-6.

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Kampschulte, Marian, Thomas Buch, Rainer Bohle, and Alexander Langheinrich. "Vasa vasorum and atherosclerosis – Quid novi?" Thrombosis and Haemostasis 97, no. 06 (2007): 873–79. http://dx.doi.org/10.1160/th06-12-0742.

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SummaryThe role of vasa vasorum (VV) in atherosclerosis is hotly debated, and new experimental techniques have recently opened an opportunity to take a fresh look at this important topic. Although the proliferation of VV due to atherogenic stimuli is controversial, experimental and clinical evidence strongly suggest the potential of VV in vascular proliferative disorders. In the past, paradigms of atherosclerosis and restenosis have excluded the adventitia and VV in the artery wall due, in part, to a lack of i) appropriate animal models featuring adventitial VV neovascularization, ii) imaging technologies to quantitate adventitial VV and plaque neovascularization and iii) its consequences, concerning information on detectable plaque substrate in vulnerable lesions. VV proliferation is associated with increasing plaque burden and is linked to cellular processes which are critical during the development of atherosclerotic plaques such as inflammation, plaque perfusion and concomitant intraplaque hemorrhage – but the regulation and induction of VV based on pathological settings are poorly understood. This review discusses the current scientific status and its controversies and identifies open research questions.

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Brinjikji, Waleed, Alejandro A. Rabinstein, Giuseppe Lanzino, Mohammad H. Murad, Eric E. Williamson, J. Kevin DeMarco, and John Huston III. "Ultrasound Characteristics of Symptomatic Carotid Plaques: A Systematic Review and Meta-Analysis." Cerebrovascular Diseases 40, no. 3-4 (2015): 165–74. http://dx.doi.org/10.1159/000437339.

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Background: Ultrasound is the most commonly used imaging modality for assessing carotid artery stenosis. A number of studies have demonstrated that surface irregularities, heterogeneous echotexture and hypoechoic plaques are risk factors for acute ischemic stroke. We performed a systematic review and meta-analysis of the literature to better define the risk of stroke based on the sonographic characteristics of carotid plaques. Materials and Methods: We performed a comprehensive search for studies reporting imaging findings of symptomatic and asymptomatic carotid plaques on ultrasound using MEDLINE and EMBASE. We included both case-control and cohort studies examining the relationship between complex plaque and acute ischemic stroke or transient ischemic attack. Complex plaque was defined as plaque that had any of the following characteristics: heterogeneous echogenicity, echolucency, neovascularization, surface irregularity, ulceration, and intraplaque motion. Meta-analyses using the random-effects model were performed for complex plaque and each of the individual complex plaque characteristics. p < 0.05 was considered statistically significant. We explored the impact of publication bias by constructing funnel plots and testing their symmetry. We conducted the meta-analysis using Comprehensive Meta-analysis version 2.2, Englewood, N.J., USA. Results: A total of 1,013 articles were screened and 23 studies with 6,706 carotid plaques were included. Ultrasound plaque characteristics with a higher prevalence in individuals with symptomatic compared to asymptomatic carotid artery stenosis included plaque neovascularity (OR = 19.68, 95% CI = 3.14-123.16), complex plaque (OR = 5.12, 95% CI = 3.42-7.67), plaque ulceration (OR = 3.58, 95% CI = 1.66-7.71), plaque echolucency (OR = 3.99, 95% CI = 3.06-5.19) and intraplaque motion (OR = 1.57, 95% CI = 1.02-2.41). Variables not associated with symptom status included heterogenous echotexture (OR = 2.68, 95% CI = 0.56-12.80) and surface irregularity without ulceration (OR = 2.38, 95% CI = 0.70-8.11). No evidence of publication bias was observed based on Eggers test (p value of 0.05 for complex plaque and 0.53 for plaque echolucency). The remaining plaque features had insufficient data to assess for publication bias. Conclusions: Our meta-analysis and systematic review of the literature demonstrated that plaques with complex features, particularly those with echolucency, neovascularization, ulceration and intraplaque motion are associated with ischemic symptoms. Assessment of carotid plaque on ultrasound may provide stroke risk information beyond measurement of luminal stenosis. Thus, sonographic evaluation of carotid artery stenosis should focus on the detection of these plaque characteristics in addition to quantifying the degree of stenosis.

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Chung, Hyemoon, Bu Yong Kim, Hyun Soo Kim, Hyung Oh Kim, Jung Myung Lee, Jong Shin Woo, Jin Bae Kim, Woo-Shik Kim, Kwon Sam Kim, and Weon Kim. "Long-Term Clinical Effects of Carotid Intraplaque Neovascularization in Patients with Coronary Artery Disease." Korean Journal of Radiology 21, no. 7 (2020): 900. http://dx.doi.org/10.3348/kjr.2019.0550.

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Zaman, Raiyan Tripti, Hisanori Kosuge, Sanjiv Sam Gambhir, and Lei Xing. "Detection of Carotid Artery Stenosis with Intraplaque Hemorrhage and Neovascularization Using a Scanning Interferometer." Nano Letters 21, no. 13 (June 22, 2021): 5714–21. http://dx.doi.org/10.1021/acs.nanolett.1c01441.

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Song, Yan, Ying Dang, Hui Cai, Jichang Wang, Bo Liu, Jun Feng, and Litao Ruan. "Carotid intraplaque neovascularization predicts atherosclerotic renal artery stenosis in patients with carotid artery stenosis." Nutrition, Metabolism and Cardiovascular Diseases 30, no. 9 (August 2020): 1492–99. http://dx.doi.org/10.1016/j.numecd.2020.04.031.

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Song, Y., Y. Dang, L. L. Dang, C. Zhao, J. Zheng, J. Feng, and L. T. Ruan. "Association between intraplaque neovascularization assessed by contrast-enhanced ultrasound and the risk of stroke." Clinical Radiology 75, no. 1 (January 2020): 70–75. http://dx.doi.org/10.1016/j.crad.2019.08.019.

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Camaré, Caroline, Corinne Vanucci-Bacqué, Nathalie Augé, Mélanie Pucelle, Corinne Bernis, Audrey Swiader, Michel Baltas, Florence Bedos-Belval, Robert Salvayre, and Anne Nègre-Salvayre. "4-Hydroxynonenal Contributes to Angiogenesis through a Redox-Dependent Sphingolipid Pathway: Prevention by Hydralazine Derivatives." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–11. http://dx.doi.org/10.1155/2017/9172741.

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The neovascularization of atherosclerotic lesions is involved in plaque development and may contribute to intraplaque hemorrhage and plaque fragilization and rupture. Among the various proangiogenic agents involved in the neovascularization process, proatherogenic oxidized LDLs (oxLDLs) contribute to the formation of tubesviathe generation of sphingosine 1-phosphate (S1P), a major mitogenic and proangiogenic sphingolipid mediator. In this study, we investigated whether 4-hydroxynonenal (4-HNE), an aldehydic lipid oxidation product abundantly present in oxLDLs, contributes to their proangiogenic properties. Immunofluorescence analysis of human atherosclerotic lesions from carotid endarterectomy showed the colocalization of HNE-adducts with CD31, a marker of endothelial cells, suggesting a close relationship between 4-HNE and neovessel formation. In vitro, low 4-HNE concentration (0.5–1 µM) elicited the formation of tubes by human microvascular endothelial cells (HMEC-1), whereas higher concentrations were not angiogenic. The formation of tubes by 4-HNE involved the generation of reactive oxygen species and the activation of the sphingolipid pathway, namely, the neutral type 2 sphingomyelinase and sphingosine kinase-1 (nSMase2/SK-1) pathway, indicating a role for S1P in the angiogenic signaling of 4-HNE. Carbonyl scavengers hydralazine and bisvanillyl-hydralazone inhibited the nSMase2/SK1 pathway activation and the formation of tubes on Matrigel® evoked by 4-HNE. Altogether, these results emphasize the role of 4-HNE in the angiogenic effect of oxLDLs and point out the potential interest of pharmacological carbonyl scavengers to prevent the neovascularization process.

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Mantella, Laura, Kayla N. Colledanchise, Marie-France Hetu, Julia Herr, Mitchell Wheatley, Steven Feinstein, and Amer M. Johri. "CAROTID PLAQUE TISSUE COMPOSITION IS RELATED TO INTRAPLAQUE NEOVASCULARIZATION IN PATIENTS WITH ACUTE CORONARY SYNDROME." Journal of the American College of Cardiology 77, no. 18 (May 2021): 1356. http://dx.doi.org/10.1016/s0735-1097(21)02714-5.

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Lyu, Qi, Zehao Liu, Zewen Zhu, and Ming Yin. "Neutrophil‐to‐lymphocyte ratio is associated with carotid intraplaque neovascularization in asymptomatic carotid stenosis patients." Journal of Clinical Ultrasound 50, no. 3 (December 31, 2021): 319–25. http://dx.doi.org/10.1002/jcu.23132.

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YUAN, HONG, HAIQIANG HU, JINDONG SUN, MINGJUAN SHI, HUAMIN YU, CAIRONG LI, YU SUN, ZHIJIAN YANG, and ROBERT M. HOFFMAN. "Ultrasound Microbubble Delivery Targeting Intraplaque Neovascularization Inhibits Atherosclerotic Plaque in an APOE-deficient Mouse Model." In Vivo 32, no. 5 (2018): 1025–32. http://dx.doi.org/10.21873/invivo.11342.

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Kim, Weon, Hyun Soo Kim, Won Yu Kang, Jin Bae Kim, and Woo Shik Kim. "BIOCHEMICAL AND CLINICAL CORRELATION OF INTRAPLAQUE NEOVASCULARIZATION USING CONTRAST-ENHANCED ULTRASOUND OF THE CAROTID ARTERY." Journal of the American College of Cardiology 63, no. 12 (April 2014): A2111. http://dx.doi.org/10.1016/s0735-1097(14)62114-8.

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Wang, Yuxuan, Chao Jiang, Hui Huang, Niu Liu, Yi Wang, Zhaoyao Chen, Sen Liang, et al. "Correlation of Cerebral White Matter Lesions with Carotid Intraplaque Neovascularization assessed by Contrast-enhanced Ultrasound." Journal of Stroke and Cerebrovascular Diseases 29, no. 8 (August 2020): 104928. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104928.

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Kurdi, Ammar, Lynn Roth, Bieke Van der Veken, Debby Van Dam, Peter P. De Deyn, Mireille De Doncker, Hugo Neels, Guido R. Y. De Meyer, and Wim Martinet. "Everolimus depletes plaque macrophages, abolishes intraplaque neovascularization and improves survival in mice with advanced atherosclerosis." Vascular Pharmacology 113 (February 2019): 70–76. http://dx.doi.org/10.1016/j.vph.2018.12.004.

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