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Artykuły w czasopismach na temat "Pathological hypertrophy"
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Li, Wei-ming, Yi-fan Zhao, Guo-fu Zhu, Wen-hui Peng, Meng-yun Zhu, Xue-jing Yu, Wei Chen, Da-chun Xu i Ya-wei Xu. "Dual specific phosphatase 12 ameliorates cardiac hypertrophy in response to pressure overload". Clinical Science 131, nr 2 (23.12.2016): 141–54. http://dx.doi.org/10.1042/cs20160664.
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Pathological cardiac hypertrophy is an independent risk factor of heart failure. However, we still lack effective methods to reverse cardiac hypertrophy. DUSP12 is a member of the dual specific phosphatase (DUSP) family, which is characterized by its DUSP activity to dephosphorylate both tyrosine and serine/threonine residues on one substrate. Some DUSPs have been identified as being involved in the regulation of cardiac hypertrophy. However, the role of DUSP12 during pathological cardiac hypertrophy is still unclear. In the present study, we observed a significant decrease in DUSP12 expression in hypertrophic hearts and cardiomyocytes. Using a genetic loss-of-function murine model, we demonstrated that DUSP12 deficiency apparently aggravated pressure overload-induced cardiac hypertrophy and fibrosis as well as impaired cardiac function, whereas cardiac-specific overexpression of DUPS12 was capable of reversing this hypertrophic and fibrotic phenotype and improving contractile function. Furthermore, we demonstrated that JNK1/2 activity but neither ERK1/2 nor p38 activity was increased in the DUSP12 deficient group and decreased in the DUSP12 overexpression group both in vitro and in vivo under hypertrophic stress conditions. Pharmacological inhibition of JNK1/2 activity (SP600125) is capable of reversing the hypertrophic phenotype in DUSP12 knockout (KO) mice. DUSP12 protects against pathological cardiac hypertrophy and related pathologies. This regulatory role of DUSP12 is primarily through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 could be a promising therapeutic target of pathological cardiac hypertrophy. DUSP12 is down-regulated in hypertrophic hearts. An absence of DUSP12 aggravated cardiac hypertrophy, whereas cardiomyocyte-specific DUSP12 overexpression can alleviate this hypertrophic phenotype with improved cardiac function. Further study demonstrated that DUSP12 inhibited JNK activity to attenuate pathological cardiac hypertrophy.
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Yu, Qing, Wenxin Kou, Xu Xu, Shunping Zhou, Peipei Luan, Xiaopeng Xu, Hailing Li i in. "FNDC5/Irisin inhibits pathological cardiac hypertrophy". Clinical Science 133, nr 5 (1.03.2019): 611–27. http://dx.doi.org/10.1042/cs20190016.
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Abstract Cardiac hypertrophy is a common pathophysiological process in various cardiovascular diseases, which still has no effective therapies. Irisin is a novel myokine mainly secreted by skeletal muscle and is believed to be involved in the regulation of energy metabolism. In the present study, we found that irisin expression was elevated in hypertrophic murine hearts and serum. Moreover, angiotension II-induced cardiomyocyte hypertrophy was attenuated after irisin administration and aggravated after irisin knockdown in vitro. Next, we generated transverse aortic constriction (TAC)-induced cardiac hypertrophy murine model and found that cardiac hypertrophy and fibrosis were significantly attenuated with improved cardiac function assessed by echocardiography after irisin treatment. Mechanistically, we demonstrated that FNDC5 was cleaved into irisin, at least partially, in a disintegrin and metalloproteinase (ADAM) family-dependent manner. ADAM10 was the candidate enzyme responsible for the cleavage. Further, we found irisin treatment activated AMPK and subsequently inhibited activation of mTOR. AMPK inhibition ablated the protective role of irisin administration. In conclusion, we find irisin is secreted in an ADAM family-dependent manner, and irisin treatment improves cardiac function and attenuates pressure overload-induced cardiac hypertrophy and fibrosis mainly through regulating AMPK-mTOR signaling.
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Kang, Peter M., Patrick Yue, Zhilin Liu, Oleg Tarnavski, Natalya Bodyak i Seigo Izumo. "Alterations in apoptosis regulatory factors during hypertrophy and heart failure". American Journal of Physiology-Heart and Circulatory Physiology 287, nr 1 (lipiec 2004): H72—H80. http://dx.doi.org/10.1152/ajpheart.00556.2003.
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Cardiac hypertrophy from pathological stimuli often proceeds to heart failure, whereas cardiac hypertrophy from physiological stimuli does not. In this study, physiological hypertrophy was created by a daily exercise regimen and pathological hypertrophy was created from a high-salt diet in Dahl salt-sensitive rats. The rats continued on a high-salt diet progressed to heart failure associated with an increased rate of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cardiomyocytes. We analyzed primary cultures of these hearts and found that only cardiomyocytes made hypertrophic by a pathological stimulus show increased sensitivity to apoptosis. Examination of the molecular changes associated with these distinct types of hypertrophy revealed changes in Bcl-2 family members and caspases favoring survival during physiological hypertrophy. However, in pathological hypertrophy, there were more diffuse proapoptotic changes, including changes in Fas, the Bcl-2 protein family, and caspases. Therefore, we speculate that this increased sensitivity to apoptotic stimulation along with proapoptotic changes in the apoptosis program may contribute to the development of heart failure seen in pathological cardiac hypertrophy.
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Li, Peng-Long, Hui Liu, Guo-Peng Chen, Ling Li, Hong-Jie Shi, Hong-Yu Nie, Zhen Liu i in. "STEAP3 (Six-Transmembrane Epithelial Antigen of Prostate 3) Inhibits Pathological Cardiac Hypertrophy". Hypertension 76, nr 4 (październik 2020): 1219–30. http://dx.doi.org/10.1161/hypertensionaha.120.14752.
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Pathological cardiac hypertrophy is one of the major predictors and inducers of heart failure, the end stage of various cardiovascular diseases. However, the molecular mechanisms underlying pathogenesis of pathological cardiac hypertrophy remain largely unknown. Here, we provided the first evidence that STEAP3 (Six-Transmembrane Epithelial Antigen of Prostate 3) is a key negative regulator of this disease. We found that the expression of STEAP3 was reduced in pressure overload-induced hypertrophic hearts and phenylephrine-induced hypertrophic cardiomyocytes. In a transverse aortic constriction-triggered mouse cardiac hypertrophy model, STEAP3 deficiency remarkably deteriorated cardiac hypertrophy and fibrosis, whereas the opposite phenotype was observed in the cardiomyocyte-specific STEAP3 overexpressing mice. Accordingly, STEAP3 significantly mitigated phenylephrine-induced cell enlargement in primary neonatal rat cardiomyocytes. Mechanistically, via RNA-seq and immunoprecipitation-mass screening, we demonstrated that STEAP3 directly bond to Rho family small GTPase 1 and suppressed the activation of downstream mitogen-activated protein kinase-extracellular signal-regulated kinase signaling cascade. Remarkably, the antihypertrophic effect of STEAP3 was largely blocked by overexpression of constitutively active mutant Rac1 (G12V). Our study indicates that STEAP3 serves as a novel negative regulator of pathological cardiac hypertrophy by blocking the activation of the Rac1-dependent signaling cascade and may contribute to exploring effective therapeutic strategies of pathological cardiac hypertrophy treatment.
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JACOB, R., M. VOGT i H. RUPP. "Physiological and pathological hypertrophy*". Journal of Molecular and Cellular Cardiology 18 (1986): 35. http://dx.doi.org/10.1016/s0022-2828(86)80135-3.
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Tanaka, M., H. Fujiwara i C. Kawai. "Pathological features of hypertrophic cardiomyopathy without asymmetrical septal hypertrophy." Heart 56, nr 3 (1.09.1986): 294–97. http://dx.doi.org/10.1136/hrt.56.3.294.
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Hu, Chengyun, Feibiao Dai, Jiawu Wang, Lai Jiang, Di Wang, Jie Gao, Jun Huang i in. "Peroxiredoxin-5 Knockdown Accelerates Pressure Overload-Induced Cardiac Hypertrophy in Mice". Oxidative Medicine and Cellular Longevity 2022 (29.01.2022): 1–12. http://dx.doi.org/10.1155/2022/5067544.
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A recent study showed that peroxiredoxins (Prxs) play an important role in the development of pathological cardiac hypertrophy. However, the involvement of Prx5 in cardiac hypertrophy remains unclear. Therefore, this study is aimed at investigating the role and mechanisms of Prx5 in pathological cardiac hypertrophy and dysfunction. Transverse aortic constriction (TAC) surgery was performed to establish a pressure overload-induced cardiac hypertrophy model. In this study, we found that Prx5 expression was upregulated in hypertrophic hearts and cardiomyocytes. In addition, Prx5 knockdown accelerated pressure overload-induced cardiac hypertrophy and dysfunction in mice by activating oxidative stress and cardiomyocyte apoptosis. Importantly, heart deterioration caused by Prx5 knockdown was related to mitogen-activated protein kinase (MAPK) pathway activation. These findings suggest that Prx5 could be a novel target for treating cardiac hypertrophy and heart failure.
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Lu, Dan, Jizheng Wang, Jing Li, Feifei Guan, Xu Zhang, Wei Dong, Ning Liu, Shan Gao i Lianfeng Zhang. "Meox1 accelerates myocardial hypertrophic decompensation through Gata4". Cardiovascular Research 114, nr 2 (16.11.2017): 300–311. http://dx.doi.org/10.1093/cvr/cvx222.
Pełny tekst źródłaStreszczenie:
AbstractAimsPathological hypertrophy is the result of gene network regulation, which ultimately leads to adverse cardiac remodelling and heart failure (HF) and is accompanied by the reactivation of a ‘foetal gene programme’. The Mesenchyme homeobox 1 (Meox1) gene is one of the foetal programme genes. Meox1 may play a role in embryonic development, but its regulation of pathological hypertrophy is not known. Therefore, this study investigated the effect of Meox1 on pathological hypertrophy, including familial and pressure overload-induced hypertrophy, and its potential mechanism of action.Methods and resultsMeox1 expression was markedly down-regulated in the wild-type adult mouse heart with age, and expression was up-regulated in heart tissues from familial dilated cardiomyopathy (FDCM) mice of the cTnTR141W strain, familial hypertrophic cardiomyopathy (FHCM) mice of the cTnTR92Q strain, pressure overload-induced HF mice, and hypertrophic cardiomyopathy (HCM) patients. Echocardiography, histopathology, and hypertrophic molecular markers consistently demonstrated that Meox1 overexpression exacerbated the phenotypes in FHCM and in mice with thoracic aorta constriction (TAC), and that Meox1 knockdown improved the pathological changes. Gata4 was identified as a potential downstream target of Meox1 using digital gene expression (DGE) profiling, real-time PCR, and bioinformatics analysis. Promoter activity data and chromatin immunoprecipitation (ChIP) and Gata4 knockdown analyses indicated that Meox1 acted via activation of Gata4 transcription.ConclusionMeox1 accelerated decompensation via the downstream target Gata4, at least in part directly. Meox1 and other foetal programme genes form a highly interconnected network, which offers multiple therapeutic entry points to dampen the aberrant expression of foetal genes and pathological hypertrophy.
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Gao, Si, Xue-ping Liu, Li-hua Wei, Jing Lu i Peiqing Liu. "Upregulation of α-enolase protects cardiomyocytes from phenylephrine-induced hypertrophy". Canadian Journal of Physiology and Pharmacology 96, nr 4 (kwiecień 2018): 352–58. http://dx.doi.org/10.1139/cjpp-2017-0282.
Pełny tekst źródłaStreszczenie:
Cardiac hypertrophy often refers to the abnormal growth of heart muscle through a variety of factors. The mechanisms of cardiomyocyte hypertrophy have been extensively investigated using neonatal rat cardiomyocytes treated with phenylephrine. α-Enolase is a glycolytic enzyme with “multifunctional jobs” beyond its catalytic activity. Its possible contribution to cardiac dysfunction remains to be determined. The present study aimed to investigate the change of α-enolase during cardiac hypertrophy and explore its role in this pathological process. We revealed that mRNA and protein levels of α-enolase were significantly upregulated in hypertrophic rat heart induced by abdominal aortic constriction and in phenylephrine-treated neonatal rat cardiomyocytes. Furthermore, knockdown of α-enolase by RNA interference in cardiomyocytes mimicked the hypertrophic responses and aggravated phenylephrine-induced hypertrophy without reducing the total glycolytic activity of enolase. In addition, knockdown of α-enolase led to an increase of GATA4 expression in the normal and phenylephrine-treated cardiomyocytes. Our results suggest that the elevation of α-enolase during cardiac hypertrophy is compensatory. It exerts a catalytic independent role in protecting cardiomyocytes against pathological hypertrophy.
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Luckey, Stephen W., Chris D. Haines, John P. Konhilas, Elizabeth D. Luczak, Antke Messmer-Kratzsch i Leslie A. Leinwand. "Cyclin D2 is a critical mediator of exercise-induced cardiac hypertrophy". Experimental Biology and Medicine 242, nr 18 (13.09.2017): 1820–30. http://dx.doi.org/10.1177/1535370217731503.
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A number of signaling pathways underlying pathological cardiac hypertrophy have been identified. However, few studies have probed the functional significance of these signaling pathways in the context of exercise or physiological pathways. Exercise studies were performed on females from six different genetic mouse models that have been shown to exhibit alterations in pathological cardiac adaptation and hypertrophy. These include mice expressing constitutively active glycogen synthase kinase-3β (GSK-3βS9A), an inhibitor of CaMK II (AC3-I), both GSK-3βS9A and AC3-I (GSK-3βS9A/AC3-I), constitutively active Akt (myrAkt), mice deficient in MAPK/ERK kinase kinase-1 (MEKK1−/−), and mice deficient in cyclin D2 (cyclin D2−/−). Voluntary wheel running performance was similar to NTG littermates for five of the mouse lines. Exercise induced significant cardiac growth in all mouse models except the cyclin D2−/− mice. Cardiac function was not impacted in the cyclin D2−/− mice and studies using a phospho-antibody array identified six proteins with increased phosphorylation (greater than 150%) and nine proteins with decreased phosphorylation (greater than 33% decrease) in the hearts of exercised cyclin D2−/− mice compared to exercised NTG littermate controls. Our results demonstrate that unlike the other hypertrophic signaling molecules tested here, cyclin D2 is an important regulator of both pathologic and physiological hypertrophy. Impact statement This research is relevant as the hypertrophic signaling pathways tested here have only been characterized for their role in pathological hypertrophy, and not in the context of exercise or physiological hypertrophy. By using the same transgenic mouse lines utilized in previous studies, our findings provide a novel and important understanding for the role of these signaling pathways in physiological hypertrophy. We found that alterations in the signaling pathways tested here had no impact on exercise performance. Exercise induced cardiac growth in all of the transgenic mice except for the mice deficient in cyclin D2. In the cyclin D2 null mice, cardiac function was not impacted even though the hypertrophic response was blunted and a number of signaling pathways are differentially regulated by exercise. These data provide the field with an understanding that cyclin D2 is a key mediator of physiological hypertrophy.
Rozprawy doktorskie na temat "Pathological hypertrophy"
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Crampton, Matthew S., i n/a. "Differential Gene Expression in Pathological and Physiological Cardiac Hypertrophy". Griffith University. School of Biomolecular and Biomedical Science, 2006. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20070104.165826.
Pełny tekst źródłaStreszczenie:
Cardiac hypertrophy defines an adaptive process brought about in response to sustained increases in haemodynamic work. Cardiomyocytes undergo an initial compensatory phase in which enlargement and contractility alterations normalise wall stress and maintain adequate perfusion of organs. In pathological hypertrophy, this deteriorates to a decompensated state characterised by ventricular dysfunction and predisposition to heart failure. In contrast, physiological hypertrophy and associated enhanced cardiac functioning arising from chronic exercise training does not progress to heart failure. Determination of the molecular pathways underlying myocardial hypertrophy remains a challenge for cardiovascular research. The objective of the work presented in this thesis was to identify genes differentially expressed during pathological and physiological hypertrophy in order to enhance our knowledge of the mechanistic processes involved. A reverse Northern hybridisation method was applied to profile the expression of specifically selected genes in the hypertrophic models examined. Functional categories represented in the gene panel assembled included cardiac contractile and cytoskeletal markers, matrix metalloproteinases, vasoactive pathway factors, calcium handling genes, ion channels, cardiac regulatory factors, signalling pathway intermediates, apoptotic factors and histone deacetylases. In order to investigate pathological hypertrophy, a deoxycorticosterone acetate-salt (DOCA-salt) rat model was utilised. DOCA-salt treated rats used in this study demonstrated a 1.4-fold increase in heart weight to body weight ratio compared to controls. Impaired cardiac function indicative of a decompensated pathological phenotype in the DOCA-salt treated group was demonstrated by way of decreased chamber size, impaired myocardial compliance and significantly reduced cardiac output. Reverse Northern hybridisation analysis of 95 selected genes identified a number of candidates with differential expression in hearts of DOCA-salt treated rats. Increased gene expression was demonstrated for the collagenase MMP1 and stress-activated signal transduction factor Sin1. In contrast, the sarcoplasmic reticulum calcium ATPase SERCA-2 and anti-apoptotic factor BCL2l-10 genes exhibited decreased expression. To investigate changes in gene expression associated with physiological hypertrophy, use was made of an endurance run-trained rat model. The run-trained rats used in this study demonstrated a 24.1% increase in heart weight to body weight ratio and improvements in performance consistent with physiological cardiac adaptation. These performance indicators included improvements in systolic volume, cardiac output, myocardial compliance and bio-energetic function. Reverse Northern hybridisation expression analysis of 56 genes identified a number of differentially expressed mRNA transcripts in run-trained hypertrophied hearts. Four genes shown to demonstrate reduced expression in the run-trained rat model were interleukin-1 receptor associated kinase (IRAK1) and the developmentally expressed transcription factors Nkx-2.3, dHAND, and IRX-2. Based upon the reverse Northern hybridisation results, four genes were selected for Western blotting analysis of rat cardiac tissue. Of these, MMP1 and a putative isoform of Sin1 exhibited increased levels in DOCA-salt treated hypertrophic left ventricular tissue, results that correlate with the findings of increased mRNA expression for these two genes. Therefore, this study identified MMP1 and Sin1 as candidates involved in pathological but not physiological hypertrophy. This finding is in accord with other recent investigations demonstrating that pathological hypertrophy and physiological hypertrophy are associated with distinct molecular phenotypes. An aside to the major objective of identifying genes differentially regulated in left ventricular hypertrophy involved the application of the P19CL6 cell in vitro model of cardiomyogenesis to compare protein expression during hypertrophy and development. The Sin1 isoform, found to be up-regulated during DOCA-salt induced hypertrophy, was also shown to be more abundant in differentiating, than non-differentiating, P19CL6 cells. This result is consistent with the developing paradigm that implicates 'fetal' genes in the hypertrophic remodelling process.
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Crampton, Matthew S. "Differential Gene Expression in Pathological and Physiological Cardiac Hypertrophy". Thesis, Griffith University, 2006. http://hdl.handle.net/10072/366605.
Pełny tekst źródłaStreszczenie:
Cardiac hypertrophy defines an adaptive process brought about in response to sustained increases in haemodynamic work. Cardiomyocytes undergo an initial compensatory phase in which enlargement and contractility alterations normalise wall stress and maintain adequate perfusion of organs. In pathological hypertrophy, this deteriorates to a decompensated state characterised by ventricular dysfunction and predisposition to heart failure. In contrast, physiological hypertrophy and associated enhanced cardiac functioning arising from chronic exercise training does not progress to heart failure. Determination of the molecular pathways underlying myocardial hypertrophy remains a challenge for cardiovascular research. The objective of the work presented in this thesis was to identify genes differentially expressed during pathological and physiological hypertrophy in order to enhance our knowledge of the mechanistic processes involved. A reverse Northern hybridisation method was applied to profile the expression of specifically selected genes in the hypertrophic models examined. Functional categories represented in the gene panel assembled included cardiac contractile and cytoskeletal markers, matrix metalloproteinases, vasoactive pathway factors, calcium handling genes, ion channels, cardiac regulatory factors, signalling pathway intermediates, apoptotic factors and histone deacetylases. In order to investigate pathological hypertrophy, a deoxycorticosterone acetate-salt (DOCA-salt) rat model was utilised. DOCA-salt treated rats used in this study demonstrated a 1.4-fold increase in heart weight to body weight ratio compared to controls. Impaired cardiac function indicative of a decompensated pathological phenotype in the DOCA-salt treated group was demonstrated by way of decreased chamber size, impaired myocardial compliance and significantly reduced cardiac output. Reverse Northern hybridisation analysis of 95 selected genes identified a number of candidates with differential expression in hearts of DOCA-salt treated rats. Increased gene expression was demonstrated for the collagenase MMP1 and stress-activated signal transduction factor Sin1. In contrast, the sarcoplasmic reticulum calcium ATPase SERCA-2 and anti-apoptotic factor BCL2l-10 genes exhibited decreased expression. To investigate changes in gene expression associated with physiological hypertrophy, use was made of an endurance run-trained rat model. The run-trained rats used in this study demonstrated a 24.1% increase in heart weight to body weight ratio and improvements in performance consistent with physiological cardiac adaptation. These performance indicators included improvements in systolic volume, cardiac output, myocardial compliance and bio-energetic function. Reverse Northern hybridisation expression analysis of 56 genes identified a number of differentially expressed mRNA transcripts in run-trained hypertrophied hearts. Four genes shown to demonstrate reduced expression in the run-trained rat model were interleukin-1 receptor associated kinase (IRAK1) and the developmentally expressed transcription factors Nkx-2.3, dHAND, and IRX-2. Based upon the reverse Northern hybridisation results, four genes were selected for Western blotting analysis of rat cardiac tissue. Of these, MMP1 and a putative isoform of Sin1 exhibited increased levels in DOCA-salt treated hypertrophic left ventricular tissue, results that correlate with the findings of increased mRNA expression for these two genes. Therefore, this study identified MMP1 and Sin1 as candidates involved in pathological but not physiological hypertrophy. This finding is in accord with other recent investigations demonstrating that pathological hypertrophy and physiological hypertrophy are associated with distinct molecular phenotypes. An aside to the major objective of identifying genes differentially regulated in left ventricular hypertrophy involved the application of the P19CL6 cell in vitro model of cardiomyogenesis to compare protein expression during hypertrophy and development. The Sin1 isoform, found to be up-regulated during DOCA-salt induced hypertrophy, was also shown to be more abundant in differentiating, than non-differentiating, P19CL6 cells. This result is consistent with the developing paradigm that implicates 'fetal' genes in the hypertrophic remodelling process.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
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Ferreira, Linda. "A Molecular Analysis of Cardiac Hypertrophy". Thesis, Griffith University, 2007. http://hdl.handle.net/10072/367757.
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Abstract :Cardiac hypertrophy has been identified as the most important independent risk factor
for cardiovascular-related morbidity and mortality and is therefore regarded as
a pathological condition. Despite this, beneficial physiological forms also appear to
exist, such as in response to exercise, leading to maintained or improved cardiac
function. The aim of this thesis was to examine two distinct rodent models, an endurance
run-trained rat, and the DOCA-salt hypertensive rat, representing physiological
and pathological hypertrophy, respectively, in order to develop a better understanding
of the molecular changes associated with each condition. The thesis also examined
the effect of dietary supplementation of L-arginine to the pathological model,
a treatment that has been shown to ameliorate/prevent many of the cardiovascular
impairments. Studies examined selected candidate genes (qRT-PCR), including conventional
biomarkers of hypertrophy and exploratory analysis of adenosine-related
genes (given adenosine’s established regulatory and protective role in the heart, yet
minimally studied in cardiac hypertrophy), and explored global transcriptomic shifts
via microarrays. The hypothesis of this work was that cardiac hypertrophy lies on
a continuum, with similarities existing at the cardiac transcriptional level between
early (adaptive) stages of pathological hypertrophy (DOCA-salt rat) and later stages
of physiological hypertrophy (endurance run-trained rat).
Examination of ten biomarkers of hypertrophy (ANF, BNP, -MHC, -MHC, cardiac
-actin, skeletal -actin, SERCA2, PPAR, Coll I and III) revealed that the pathological
model displayed alterations in the expression of many of these molecules in
line with the literature. These changes were not observed in the physiological model.
This therefore reinforces the value of conventional biomarkers in delineating pathological
vs. physiological hypertrophies, and reveals fundamental differences in genesis
of these two forms of hypertrophy.
The adenosine system (receptors and purine handling molecules) was altered in
the pathological hypertrophy model as evidenced by the modulation of genes corresponding
to A3AR, Ada, and Adk, with a potential shift from purine salvage towards
degradation of adenosine to inosine. Furthermore, this study represents the
first report of altered regulation of the nucleoside transporter ENT3 in a pathological
condition. None of these changes were seen in the physiological model with only
modulation of the A2aAR evident.
Examination of the transcriptional response to physiological hypertrophy revealed
that short (6 week) and long (12 week) training programmes resulted in different profiles,
likely reflecting progression of the hypertrophy process. The short programme
stimulated genes associated with the mitochondria, oxidoreductase, receptor binding
and coenzymemetabolismand repressed the expression of transcripts associated with
phosphorylation, catalytic activity, defence/immunity and energy pathways. Thus,
initial changes observed are primarily of a metabolic and signalling nature. In contrast,
the longer programme resulted in shifts in protein handling and synthesis, and
genes involved in structural molecule activity, nucleotide binding and cellular homeostasis.
These patterns support a progression with time from initial metabolic adaptations
to longer term shifts in protein phenotype and structural adaptations, consistent
with longer term changes in heart structure.
Similarly, the pathologicalmodel displayed different time-dependent gene expression
profiles. Overall, the pattern of changewith early (2week) treatment is suggestive
of changes in intracellular signalling and increasing transcriptional capacity with the
later changes (at 4 weeks) indicative of structural adaptations (intra- and extracellularly)
togetherwith an inflammation response. Genes coding for calciumhandling, ion
channels, and gap junctions were altered throughout themodel andmay contribute to
electrical conduction defects and cardiac dysfunction. The adrenergic signalling pathway
was modulated as associated signalling molecules were down-regulated. The
study revealed many expected and novel changes, of which further study should focus
on: calcium regulation, metabolic regulation, gap junctions, and (as might be exii
pected) signalling via the adrenergic pathway, insulin-like growth factor, PI3K, and
Jak/STAT.
L-Arginine modulated biomarker expression in pathological hypertrophy, with
stimulation of PPAR and SERCA2 with little or no effect on the adenosine-related
genes. L-Arginine affected the overall transcriptional response to DOCA-salt treatment,
stimulating genes involved in cell growth andmaintenance, nerve transmission,
heparin and glycosaminoglycan binding, peptide binding and protein targeting, as
well as the repression of genes related to apoptosis (favouring a pro-apoptotic state),
intracellular organisation and biogenesis, and enzyme inhibitor activity. The beneficial
effects of L-arginine in the setting of pathological hypertrophy may be due to
modulation of metabolism, improving calcium handling and overall enhancing cellular
functioning.
This work demonstrates that cardiac hypertrophy is clearly different at the transcriptional
level depending upon the aetiology. This repudiated the hypothesis of the
thesis that cardiac hypertrophy lies on a continuum with similarities existing at the
cardiac transcriptional level between early (adaptive) stages of pathological hypertrophy
and later stages of physiological hypertrophy. Whilst some of the data was in accordance
with current knowledge of these states, novel changes were also discovered,
contributing to our understanding of the molecular aspects of cardiac hypertrophy.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Griffith University. School of Medical Science.
Griffith Health
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Brenner, jacob Samuel. "Alternate routes of calcium entry mediating pathological cardiac hypertrophy /". May be available electronically:, 2007. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
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Loonat, Aminah Ahmed. "The involvement of p38 gamma MAPK in pathological cardiac hypertrophy". Thesis, King's College London (University of London), 2016. http://kclpure.kcl.ac.uk/portal/en/theses/the-involvement-of-p38gamma-mapk-in-pathological-cardiac-hypertrophy(f00e26a7-dab2-474d-9d3e-a52dfe9e873e).html.
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p38-mitogen activated protein kinases (p38-MAPKs) are stress activated serine/threonine kinases that are activated during several different cardiac pathologies. Classically, studies have focused solely on p38α signaling in the heart. However, there is also high cardiac expression of the p38γ isoform but little is known about its cardiac function. The aim of this study was to elucidate the signaling pathway of p38γ, with a particular focus on its role in the progression of pathological cardiac hypertrophy. Comparisons of cardiac function and structure of wild type (WT) and p38γ knock out (KO) mice, in response to abdominal aortic banding, found that KO mice developed less ventricular hypertrophy than their corresponding WT controls, and have preserved cardiac function. Basal p38γ myocardial staining was primarily localised at the membranes and throughout the cytoplasm. Following aortic constriction, nuclear staining of p38γ increased, but no accumulation of p38α was observed. This suggests that the two isoforms play distinct roles in the heart. To elucidate its signaling pathway, we generated an analogue sensitive p38γ, which is mutated at a gatekeeper residue, to specifically track and identify its endogenous substrates in the myocardium. The mutation allows only the mutant kinase, but not WT kinases, to utilise analogues of ATP that are expanded at the N6 position and contain a detectable tag on the γ-phosphate. Transfer of this tag to substrates allows subsequent isolation and identification. Furthermore, unlike other p38-MAPKs, p38γ contains a C-terminal PDZ domain interacting motif. We have utilised this motif in co pull-down assays to identify interacting proteins of p38γ in the heart. Using these techniques we have identified, amongst other substrates, LDB3 and calpastatin as novel substrates of p38γ and we have determined the residues that are targeted for phosphorylation. Lastly we have shown that phosphorylation of calpastatin reduces its efficiency as a calpain inhibitor in vitro, hence proposing a mechanism by which p38γ may mediate its pro-hypertrophic role.
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Barr, Larry A. "The Role of Calcium in the Regulation of Pathological Hypertrophy". Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/254617.
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PhysiologyPh.D.
Pathological hypertrophy leads to cardiac dysfunction and heart failure. It is not clearly defined how this process occurs in the cardiomyocyte, or how the pathology can be effectively treated. There are numerous processes that lead to pathological hypertrophy. We developed two models to study pathological hypertrophy and the role that Ca2+ plays. In one model, we administered clinical doses of the leukemia therapeutic drug imatinib to neonatal ventricular cardiomyocytes. This drug has recently been found to be cardiotoxic, and we set out to understand if Ca2+ is involved. In the second model, we developed mice with overexpression of the Ca2+ entrance channel, the L-type calcium channel (LTCC), which leads to pathological hypertrophy over time. We instituted a chronic exercise regimen on these mice to learn if physiological hypertrophy can ameliorate detrimental aspects of pathological hypertrophy. After cardiomyocytes were treated with imatinib, they expressed enhanced Ca2+ activity. Levels of atrial natriuretic peptide (ANP) were up, signifying pathological hypertrophy. We determined that Ca2+ was activating Calcineurin, leading to translocation of nuclear factor of activated T-cells (NFAT) into the nucleus, resulting in hypertrophy. This activity was blocked by Ca2+ and Calcineurin inhibitors. We concluded that imatinib causes Ca2+ induced pathological hypertrophy. When mice with LTCC overexpression were exercised, they exhibited enhanced cardiac function. They also had thicker septal walls and increased chamber diameter, hallmarks of physiological hypertrophy. Heart weight to body weight ratio was significantly higher after exercise. When isolated hearts were administered ischemia/reperfusion injury, the exercised hearts showed a significant improvement in recovery compared to sedentary LTCC overexpressed hearts. Calcium activity was enhanced at the cardiomyocyte level in both mouse lines of exercised mice. In conclusion, hearts with a pathological hypertrophic phenotype can enhance function and achieve cardioprotection through chronic exercise.
Temple University--Theses
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Harper, Shavonn Christine. "The Effects of Growth Differentiation Factor 11 on Pathological Cardiac Hypertrophy". Diss., Temple University Libraries, 2018. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/498061.
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Biomedical SciencesPh.D.
Pathological cardiac hypertrophy (PCH) occurs in response to pathological stimuli affecting the heart such as coronary artery disease, myocardial infarction, or hypertension. PCH is also be independent risk factor for cardiac events and/or sudden death. Despite therapeutic advancements in the treatment of cardiovascular diseases (CVD) and heart failure, deaths due to CVD remain the leading cause of mortality worldwide. Furthermore, treatment of these cardiovascular diseases slows their progression, but individuals eventually progress to heart failure, which has a 5-year survival rate of approximately 50 percent. There is a clear need for development of new therapies that can reverse PCH and the associated damage to the heart. As healthcare improves, populations are living longer, and illness due to age increases. One issue that occurs with aging is loss of normal cardiac function leading to heart failure. This functional decline is accompanied by morphological changes in the heart, including hypertrophy. Although it is well documented that myocardial remodeling occurs with aging, the mechanisms underlying these changes are poorly understood. Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β (TGF-β) superfamily of proteins, which regulate a number of cellular processes. Shared circulation of a young mouse with an old mouse or a single daily intraperitoneal (IP) injection of GDF11 for 30 days was shown to reverse aging-induced pathological cardiac hypertrophy. This molecule is highly homologous with another TGF-β family member, myostatin, which is a known negative growth regulator of skeletal muscle. We began by attempting to validate published data claiming that a single daily intraperitoneal (IP) injection of 0.1 mg/kg/day of GDF11 could reverse aging induced cardiac hypertrophy. We performed a blinded study during which treated 24-month-old C57BL/6 male mice with a single IP injection of 0.1 mg/kg/day of GDF11for 28 days and monitored changes in cardiac function and structure using echocardiography (ECHO). We also looked for differences in fibrosis, myocyte size, markers of pathological hypertrophy and heart weight. We were unable to find any differences between vehicle treated age mice and GDF11 treated aged mice in any of the measured parameters. While we did find an increase in heart weight between 8-week-old mice and the 24-month-old mice, there was no difference in the heart weight to body weight ratios of these groups of animals. From these data we concluded that our aged- mice did not have pathological hypertrophy and the dose of GDF11 used in this study did not have any effect on cardiac structure or function. Hypertensive heart disease results in changes in cardiac structure and function including left ventricular hypertrophy, systolic and/or diastolic dysfunction. It is also a leading cause of heart failure. Members of the TGF-β superfamily of proteins have been shown to be involved in many of the processes that occur in the heart in response to hypertension, such as the fibrotic response. Although it was previously shown that treatment with 0.1 mg/kg of GDF11 did not prevent pressure overload induced cardiac hypertrophy, we found this dose was too low to alter cardiac structure in our aging study. In addition, a single GDF11 dose is insufficient to fully address this issue. We therefore performed a blinded dose-ranging study to investigate the effects of GDF11 on pressure overload induced cardiac hypertrophy using transverse aortic constriction (TAC) which mimics the effects of chronic hypertension on the heart. In this study, animals received TAC surgery and were assigned to treatment groups so that there were no differences in wall thickness, cardiac function, or pressure gradients across the aortic constriction at the start of the treatments 1 week after TAC. Mice were given 0.5 mg/kg/day of GDF11, 1.0 mg/kg/day GDF11, 5.0 mg/kg/day of GDF11, or vehicle via a single daily IP injection for 14 days. Using these higher doses, we found that GDF11 had dose dependent effects on both cardiac structure and function following TAC. Myocyte cross sectional area was dose-dependently decreased compared to vehicle treated mice in both sham and TAC conditions. Cardiac function was preserved in the 1.0 and 5.0 mg/kg groups treatment groups after TAC. Left ventricular internal chamber dimensions were preserved with the 1.0 mg/kg treatment group. Treatment with GDF11 caused a dose dependent decrease on both body weight and heart weight in both normal and TAC mice, but with an effect on heart weight in the TAC mice that was independent of body weight. However, the 5.0 mg/kg dose caused large reductions in body weight (cachexia) and death. Our results show that GDF11 can reduce pathological hypertrophy and cardiac remodeling after pressure overload, but there is a narrow therapeutic range.
Temple University--Theses
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Sculthorpe, Nicholas. "Left ventricular long axis dynamics in pathological and physiological left ventricular hypertrophy". Thesis, University of South Wales, 2002. https://pure.southwales.ac.uk/en/studentthesis/left-ventricular-long-axis-dynamics-in-pathological-and-physiological-left-ventricular-hypertrophy(eeeb9f18-b0d5-433b-b261-2907df223717).html.
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Sub-endocardial fibres line the inner surface of both ventricles and are responsible for longitudinal oscillations of the mitral annulus, such oscillations may be measured using tissue Doppler echocardiography (IDE). During systole the annulus descends and during early diastole (ETDE) and atrial systole (ATDE) itascends. This thesis examined whether changes in the velocity of the annulus ineach of these phases of oscillation, measured using tissue Dopplerechocardiography (TDE), could determine the nature of increases in left ventricular size (pathological or physiological). Study one examined differences at rest in longitudinal velocities between individuals with hypertrophic cardiomyopathy (HCM), hypertension (HT), weightlifters, runners and controls, (n = 15 all groups) and all groups were aged between 20 - 36 years. The results demonstrated that both pathological groups had systolic and ETDE velocities significantly lower than groups with physiological hypertrophy (weightlifters or runners) or controls p < 0.05. AIDE however was not significantly different between groups. Additionally runners also demonstrated a significantly higher ETDE than either weightlifters or controls (p < 0.05). Binomial logistic regression identified longitudinal systolic velocity < 9 cm s" 1 and ETDE velocity < 11 cm s" 1 as the best combination of variables to predict pathological increases in heart size. Study two examined older subjects in order to determine whether the criteria set out in study one were applicable to senior athletes. The subject groups were the same as in study one however all subjects were aged between 36-55. In this case systolic annular velocity was significantly lower in groups with pathological LVH but ETDE < 9 cm s" 1 was a better differentiator. Binomial logistic regression identified ETDE < 9 cm s" 1 and a mitral E / A ratio < 1 as the best combination of variables to predict pathological LVH. Study three examined the age related changes in long axis function using the pooled data from studies one and two. This demonstrated that in the pathological LVH groups only ETDE / ATDE ratio was significantly correlated with age (r = - 0.5 p < 0.05) suggesting that there appears to be no summation of the effects of pathology and age on mitral annular velocities. The control groups demonstrated a significant age related reduction in all long axis variables (systolic velocity r = - 0.7 p < 0.05; ETDE r = - 0.6 p < 0.01; ATDE r = 0.5 p < 0.05; ETD E / ATDE r = - 0.5 p< 0.01). Weightlifters however did not demonstrate an age related decline in either systolic or diastolic annular velocities. Runners had no age related decline in systolic annular velocities, and whilst they had an age dependent fall in ETDE ( r = - 0.62 p < 0.05) the older runners ETDE were still significantly faster (p < 0.05) than that seen in control subjects. Study four investigated relationship between mitral annular velocity and VOiruK in runners, weightlifters and controls. These results demonstrated peak exercise E TDE strongly correlated to VO^PEAK (r = 0.8 p < 0.01). ConclusionsTaken together these data suggest that longitudinal velocities of the mitral annulus may be useful in determining the nature of increases in heart size, in addition the increased performance of endurance - trained athletes is due in part to functional changes of the long axis.
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Makarewich, Catherine Anne. "MICRODOMAIN BASED CALCIUM INFLUX PATHWAYS THAT REGULATE PATHOLOGICAL CARDIAC HYPERTROPHY AND CONTRACTILITY". Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/266828.
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Molecular and Cellular PhysiologyPh.D.
Pathological cardiac stressors, including persistent hypertension or damage from ischemic heart disease, induce a chronic demand for enhanced contractile performance of the heart. The cytosolic calcium (Ca2+) transient that regulates myocyte contraction must be persistently increased in disease states in order to maintain cardiac output to sustain the metabolic requirements of the body. Associated with this enhanced intracellular Ca2+ ([Ca2+]i) state is pathological cardiac myocyte hypertrophy, which results in large part from the activation of Ca2+-dependent activation of calcineurin (Cn)-nuclear factor of activated T cells (NFAT) signaling. The puzzling feature of this hypertrophic signaling is that the cytosolic [Ca2+] that controls contractility appears to be separate from the [Ca2+] which activates Cn-NFAT signaling. The overarching theme of this dissertation is to explore the source and spatial constraints of pathological hypertrophic signaling Ca2+ and to investigate how it is possible that sensitive and finely tuned Ca2+-dependent signaling pathways are regulated in the background of massive Ca2+ fluctuations that oscillate between 100nM and upwards of 1-2μM during each cardiac contractile cycle. L-type Ca2+ channels (LTCCs) are a major source of Ca2+ entry in cardiac myocytes and are known to play an integral role in the initiation of myocyte excitation contraction-coupling (EC-coupling). We performed a number of experiments to show that a small population of LTCCs reside outside of EC-coupling domains within caveolin (Cav-3) signaling microdomains where they provide a local source of Ca2+ to activate Cn-NFAT signaling. We designed a Cav-targeted LTCC blocker that could eliminate Cn-NFAT activation but did not reduce myocyte contractility. The activity of Cav-targeted LTCCs could also be upregulated to enhance hypertrophic signaling without affecting contractility. Therefore, we believe that caveolae-localized LTCCs do not participate in EC-coupling, but instead act locally to control the coordinated activation of Cn-NFAT signaling that drives pathological remodeling. Transient Receptor Potential (TRP) channels are also thought to provide a source of Ca2+ for activation of hypertrophic signaling. The canonical family of TRP channels (TRPC) is expressed at low levels in normal adult cardiac tissue, but these channels are upregulated in disease conditions which implicates them as stress response molecules that could potentially provide a platform for hypertrophic Ca2+ signaling. We show evidence that TRPC channel abundance and function increases in cardiac stress conditions, such as myocardial infarction (MI), and that these channels are associated with hypertrophic responses, likely through a Ca2+ microdomain effect. While we found that TRPC channels housed in caveolae membrane microdomains provides a source of [Ca2+] for induction of cardiac hypertrophy, this effect also requires interplay with LTCCs. We also found that TRPC channels have negative effects on cardiac contractility, which we believe are due to local activation of Ca2+/calmodulin-dependent protein kinase (CaMKII) and subsequent modulation of ryanodine receptors (RyRs). Further, we found that inhibiting TRPC channels in a mouse model of MI led to increased basal myocyte contractility and reduced hypertrophy and cardiac structural and functional remodeling, as well as increased survival. Collectively, the data presented in this dissertation provides comprehensive evidence that Ca2+ regulation of Cn-NFAT signaling and resultant pathological hypertrophy can be coordinated by spatially localized and regulated Ca2+ channels. The compartmentalization of LTCCs and TRPC channels in caveolae membrane microdomains along with pathological hypertrophy signaling effectors makes for an attractive explanation for how Ca2+-dependent signaling pathways are regulated under conditions of continual Ca2+ transients that mediate cardiac contraction during each heart beat. Elucidation of additional Ca2+ signaling microdomains in adult cardiac myocytes will be important in more comprehensively resolving how myocytes differentiate between signaling versus contractile Ca2+.
Temple University--Theses
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Assrafally, Farryah. "Modulation of pathological cardiac hypertrophy via the interleukin-10 signalling in the cardiomyocytes". Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-pathological-cardiac-hypertrophy-via-the-interleukin10-signalling-in-the-cardiomyocytes(430247dd-1512-4e29-9f7a-288bae85fffd).html.
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Inflammation plays a key role during pathological hypertrophy and heart failure. Whilst the roles of pro-inflammatory cytokines are relatively well understood, little is known about the anti-inflammatory cytokines in the heart. Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that is expressed in the heart and may play a crucial role during cardiac remodelling. IL-10 exerts its function by binding to the IL-10 receptor (IL-10R). The primary aim of the PhD study was to investigate the effects of the ubiquitous ablation of IL-10R1 gene during pressure overload induced hypertrophy and to characterise the downstream pathway regulated by IL-10R1 in the heart following pressure overload. The second aim was to investigate the effects of cell specific ablation of IL-10R1 in both the macrophages and cardiomyocytes during pressure overload induced hypertrophy and to identify the specific site where IL-10R1 regulates hypertrophy in the heart. During this study three mouse lines were used: IL-10R1 global knockout (IL-10R1-/-), IL-10R1 macrophage-specific knockout (IL-10R1mKO) and IL-10R1 cardiomyocyte-specific knockout (IL-10R1cKO).Mice with systemic ablation of IL-10 receptor1 (IL-10R1-/-) displayed a significant increase in hypertrophy following two weeks of transverse aortic constriction (TAC) as indicated by heart weight/tibia length ratio (HW/TL). This was accompanied by a significant increase in cardiomyocyte surface area as well as expression of hypertrophic markers such as brain natriuretic peptide (BNP) and Atrial natriuretic peptide (ANP). The IL-10R1-/- mice also had a significant increase in cardiac fibrosis when compared to the WT TAC littermates. Importantly, ejection fraction (EF) and fractional shortening (FS) were significantly reduced in IL-10R1-/- mice compared with WT littermates following TAC. The STAT3 pathway is known as the major downstream signalling pathway regulated by the IL-10R via the activation of the JAK1/STAT3 pathway. Western blot analysis showed that activation of the STAT3 signalling pathway was significantly reduced in IL-10R1-/- mice following TAC, indicating the possible involvement of this pathway. Furthermore, expression of STAT3 target genes: suppressor of cytokine signalling (SOCS3), tissue inhibitor of metalloproteinases3 (TIMP-3) and heme oxygenase (HO-1) were downregulated in the IL-10R1-/- mice following TAC. Overall the data obtain from the IL-10R1-/- mice indicate that IL-10R1 signalling plays a protective role in reducing pathological hypertrophy in the heart. Interestingly, IL-10R1mKO mice showed no difference in the hypertrophic response following TAC. Analysis of cardiac function and STAT3 activation also showed no difference between IL-10R1mKO and WT controls. This indicated that the protective effects of IL-10R1 mediated signalling during cardiac pressure overload was unlikely due to the effects in residential macrophages. In contrast, IL-10R1cKO mice displayed an elevated hypertrophic response, reduction of cardiac function and less STAT3 activation after TAC. This phenotype resembled those of IL-10R1 global knockout mice. In conclusion, this PhD study has shown that IL-10R1 mediated signalling in the heart is important in controlling pressure-overload hypertrophy. Using cell-specific knockout mice I have shown that IL-10R signalling in cardiomyocytes and not in macrophages is important in this process. These results will open a new insight in targeting IL-10 receptor in the treatment of myocardial hypertrophy in future.
Książki na temat "Pathological hypertrophy"
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D’Andrea, Antonello, André La Gerche i Christine Selton-Suty. Systemic disease and other conditions: athlete’s heart. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198726012.003.0055.
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The term ‘athlete’s heart’ refers to the structural, functional, and electrical adaptations that occur as a result of habitual exercise training. It is characterized by an increase of the internal chamber dimensions and wall thickness of both atria and ventricles. The athlete’s right ventricle also undergoes structural, functional, and electrical remodelling as a result of intense exercise training. Some research suggests that the haemodynamic stress of intense exercise is greater for the right heart and, as a result, right heart remodelling is slightly more profound when compared with the left heart. Echocardiography is the primary tool for the assessment of morphological and functional features of athlete’s heart and facilitates differentiation between physiological and pathological LV hypertrophy. Doppler myocardial and strain imaging can give additional information to the standard indices of global systolic and diastolic function and in selected cases cardiac magnetic resonance imaging may help in the diagnosis of specific myocardial diseases among athletes such as hypertrophic cardiomyopathy, dilated cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy.
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Karatasakis, G., i G. D. Athanassopoulos. Cardiomyopathies. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199599639.003.0019.
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Echocardiography is a key diagnostic method in the management of patients with cardiomyopathies.The main echocardiographic findings of hypertrophic cardiomyopathy are asymmetric hypertrophy of the septum, increased echogenicity of the myocardium, systolic anterior motion, turbulent left ventricular (LV) outflow tract blood flow, intracavitary gradient of dynamic nature, mid-systolic closure of the aortic valve and mitral regurgitation. The degree of hypertrophy and the magnitude of the obstruction have prognostic meaning. Echocardiography plays a fundamental role not only in diagnostic process, but also in management of patients, prognostic stratification, and evaluation of therapeutic intervention effects.In idiopathic dilated cardiomyopathy, echocardiography reveals dilation and impaired contraction of the LV or both ventricles. The biplane Simpson’s method incorporates much of the shape of the LV in calculation of volume; currently, three-dimensional echocardiography accurately evaluates LV volumes. Deformation parameters might be used for detection of early ventricular involvement. Stress echocardiography using dobutamine or dipyridamole may contribute to risk stratification, evaluating contractile reserve and left anterior descending flow reserve. LV dyssynchrony assessment is challenging and in patients with biventricular pacing already applied, optimization of atrio-interventricular delays should be done. Specific characteristics of right ventricular dysplasia and isolated LV non-compaction can be recognized, resulting in an increasing frequency of their prevalence. Rare forms of cardiomyopathy related with neuromuscular disorders can be studied at an earlier stage of ventricular involvement.Restrictive and infiltrative cardiomyopathies are characterized by an increase in ventricular stiffness with ensuing diastolic dysfunction and heart failure. A variety of entities may produce this pathological disturbance with amyloidosis being the most prevalent. Storage diseases (Fabry, Gaucher, Hurler) are currently treatable and early detection of ventricular involvement is of paramount importance for successful treatment. Traditional differentiation between constrictive pericarditis (surgically manageable) and the rare cases of restrictive cardiomyopathy should be properly performed.
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Kjaer, Michael, i Abigail Mackey. Muscle. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199533909.003.0002.
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Skeletal muscle is not only essential for human movement and performance, but is unfortunately also a common site for acute injuries related to physical activity and sports. The influence of exercise on skeletal muscle represents a wide range all the way from (i) physiological adaptation with regard to metabolism, morphology, and contractile properties, through (ii) physiological development of muscle hypertrophy, to (iii) pathological/physiological responses to heavy unaccustomed exercise with associated delayed onset of muscle soreness, and ending with (iv) muscle injury caused by either strain or contusion (and seldom laceration) trauma. In the present chapter we will focus on the muscle responses to acute stimuli that cause muscle injury of minor or larger magnitude, and the ensuing recovery....
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C Diaz, Eva, Celeste C Finnerty i David N. Herndon. Severe Burn Injuries and Their Long-Term Implications. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199653461.003.0016.
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Burn injury is notable for the degree and duration of pathophysiological alterations that it induces. Burn triggers profound changes in metabolism, immune function, and endocrine function, leading to a host of negative effects, including catabolism of muscle and bone and insulin resistance. These changes may persist or evolve for years after the injury has occurred, delaying recovery. This chapter discusses all of these consequences of burn injury, along with other adverse outcomes, specifically growth delay in children and hypertrophic scarring. Particular attention is placed on what is known about the mechanisms underlying each of these pathological changes and, in some cases, current practice in their management. A description is also provided of some of the pharmacologic (i.e. oxandrolone and recombinant human growth hormone) and non-pharmacologic (i.e. exercise therapy) approaches that hold promise in the treatment of burn injury and its consequences.
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Wyatt, Laura A., i Michael Doherty. Morphological aspects of pathology. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199668847.003.0003.
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Osteoarthritis (OA) is the commonest condition to affect synovial joints, but although any synovial joint can be affected, most studies of pathology relate to large joints (knees and hips). OA involves the whole joint and pathological alterations typically occur in all joint tissues. Established OA is characterized by a mixture of tissue loss and new tissue production resulting in focal loss of articular hyaline cartilage together with bone remodelling and osteophyte formation. Articular cartilage may show increased thickness in the earliest stages of OA with increased numbers of hypertrophic chondrocytes, followed by progressive decline in matrix components, thickness, and chondrocyte number. Surface fibrillation and vertical clefts become evident in mid- to end-stage OA and eventual complete loss of cartilage can occur, predominantly in maximum load-bearing regions, with subsequent eburnation and furrowing of bone. Bone remodelling may lead to alteration of bone shape and variable trabecular thickness in subchondral bone, whilst subchondral microfractures may result in localized osteonecrosis, fibrosis, and ‘cysts’. Endochondral ossification of new fibrocartilage produced predominantly at the joint margin produces characteristic bony osteophytes. The synovium shows areas of hyperplasia with varying amounts of lymphocyte aggregates and inclusion of osteochondral ‘loose’ bodies, and the outer fibrous capsule thickens to help stabilize the compromised joint. Synovial fluid increases in volume but decreases in viscosity. Periarticular changes include type II muscle atrophy and enthesophytes.
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Shirodaria, Cheerag, i Sam Dawkins. Chronic stable angina. Redaktorzy Patrick Davey i David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0089.
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Chronic stable angina is a condition where patients experience symptoms of chest pain of a particular character (e.g. angina pectoris) on effort only, due to atherosclerotic coronary artery disease. The hallmarks of stable angina are as follows. First, there must be stable atherosclerotic coronary artery disease, resulting in luminal narrowing(s) in one or more of the major epicardial coronary arteries. Atheroma can be detected by using appropriate technology. Not all angina chest discomfort is due to atherosclerotic coronary disease—some is due to aortic stenosis, and some to hypertrophic cardiomyopathy; rarely, pulmonary hypertension is the cause. Second, symptoms must have been present for some time, say, arbitrarily, 2–3 months, as opposed to the case for angina of acute coronary syndromes, where symptoms are present only for a few weeks at most (see Chapter 90). This time limit is important, as it allows the differentiation of symptoms from coronary obstruction due to coronary atheroma (generally a stable pathology, with a lower risk of infarction) from symptoms of coronary obstruction due to atheroma with superadded thrombus, which can be quite unstable and lead suddenly to total coronary obstruction with all its attendant risks. Third, symptoms must be stable, that is to say, from day to day, roughly similar levels of effort must be required for provocation. The pathological translation of this is that the degree of coronary obstruction is stable, as opposed to that of the rapidly changing coronary obstruction found in acute coronary syndromes.
Części książek na temat "Pathological hypertrophy"
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Baker, Julien S., Fergal Grace, Lon Kilgore, David J. Smith, Stephen R. Norris, Andrew W. Gardner, Robert Ringseis i in. "Pathological Cardiac Hypertrophy". W Encyclopedia of Exercise Medicine in Health and Disease, 690. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-540-29807-6_2841.
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Kalmar, Jayne M., Brigid M. Lynch, Christine M. Friedenreich, Lee W. Jones, A. N. Bosch, Alessandro Blandino, Elisabetta Toso i in. "Cardiac Hypertrophy, Pathological". W Encyclopedia of Exercise Medicine in Health and Disease, 168–71. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-540-29807-6_38.
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Cuspidi, Cesare, Laura Lonati, Lorena Sampieri, Gastone Leonetti i Alberto Zanchetti. "Physiological Versus Pathological Hypertrophy". W Advances in Experimental Medicine and Biology, 145–58. Boston, MA: Springer US, 1997. http://dx.doi.org/10.1007/978-1-4615-5385-4_16.
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Jacob, R., M. Vogt i H. Rupp. "Physiological and Pathological Hypertrophy". W Developments in Cardiovascular Medicine, 39–56. Boston, MA: Springer US, 1987. http://dx.doi.org/10.1007/978-1-4613-2051-7_2.
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Pluim, B. M., A. van der Laarse i E. E. van der Wall. "The Athlete’s Heart: A Physiological or a Pathological Phenomenon?" W Left Ventricular Hypertrophy, 85–106. Dordrecht: Springer Netherlands, 1999. http://dx.doi.org/10.1007/978-94-011-4279-3_7.
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Kato, Takao. "Genome Editing and Pathological Cardiac Hypertrophy". W Advances in Experimental Medicine and Biology, 87–101. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-19-5642-3_6.
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He, Jianfeng, Yanhong Luo, Junxia Song, Tao Tan i Hua Zhu. "Non-coding RNAs and Pathological Cardiac Hypertrophy". W Advances in Experimental Medicine and Biology, 231–45. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-1671-9_13.
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Orellana, Juan, i Alan H. Friedman. "Congenital Hypertrophy of the Retinal Pigment Epithelium". W Clinico-Pathological Atlas of Congenital Fundus Disorders, 153–55. New York, NY: Springer New York, 1993. http://dx.doi.org/10.1007/978-1-4613-9320-7_34.
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Kolwicz, Stephen C., i Rong Tian. "Fuel Metabolism Plasticity in Pathological Cardiac Hypertrophy and Failure". W Cardiac Energy Metabolism in Health and Disease, 169–82. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-1227-8_11.
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Merello, Giacomo, Luna Cavigli i Flavio D’Ascenzi. "Physiological Versus Pathological Left Ventricular Hypertrophy in the Hypertensive Athlete". W Exercise, Sports and Hypertension, 101–11. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-07958-0_7.
Pełny tekst źródłaStreszczenia konferencji na temat "Pathological hypertrophy"
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Hyekyeong Kwon, Jang-Soo Chun, Zee-Yong Park i Dong-Yu Kim. "Poster title (mass spectrometric protein profiling analyses of pathological and physiological hypertrophy cardiac muscle tissues)". W 2012 IEEE 2nd International Conference on Computational Advances in Bio and Medical Sciences (ICCABS). IEEE, 2012. http://dx.doi.org/10.1109/iccabs.2012.6182652.
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Roby, Tiffany S., i Jiro Nagatomi. "Effect of Stretch on Bladder Smooth Muscle Cells in Three-Dimensional Culture". W ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176611.
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The bladder is routinely subjected to mechanical stretch from filling cycles; however, abnormal bladder distention can result from pathological conditions such as bladder outlet obstruction. It has been suggested that abnormal mechanical environments in the bladder trigger cellular and molecular changes, such as smooth muscle cell hyperplasia or hypertrophy and alteration of the extracellular matrix (ECM). These cellular and ECM changes can, in turn, deteriorate the function of the bladder by decreasing the contractility and compliance of the tissue [1, 3, 5].
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Navitsky, Michael A., Steven Deutsch i Keefe B. Manning. "A Comparison of Thrombus Susceptibility for Two Pulsatile 50 CC Left Ventricular Assist Pumps". W ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80570.
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Approximately 5.7 million Americans are afflicted with heart disease, with a reported 670,000 new cases and 300,000 deaths each year [1]. While the success rate of transplantation procedures continues to improve, organ availability remains limited. Left ventricular assist devices (LVADs) function as a bridge to transplant for advanced staged heart failure patients awaiting a donor heart. The devices have also been used, more recently, as a bridge to recovery by helping to unload the native ventricle. Along with pharmacological intervention, LVADs can act to help reverse pathological hypertrophy and recover normal myocardial function [2].
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Dolensky, Joseph R., Lauren D. C. Casa i Ajit P. Yoganathan. "The Effect of Pulmonary Hypertension on Tricuspid Valve Coaptation in Normal and Pathologic Valve Geometries: An In Vitro Study". W ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80184.
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Pulmonary hypertension (PHTN) is a pathological condition defined as a mean pulmonary artery pressure (mPAP) greater than 25 mmHg. PHTN can result from a number of lung and heart pathologies, including abnormalities of the pulmonary vasculature, left heart disease, chronic lung disease, and chronic thrombotic disease [1]. Regardless of the cause, the increased afterload on the right heart results in right ventricle (RV) hypertrophy and dilatation and tricuspid regurgitation (TR) [2]. RV dilatation is thought to result in the displacement of the tricuspid valve (TV) papillary muscles (PM) and dilatation of the TV annulus, negatively impacting TV function.
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Baicu, Catalin F., i Michael R. Zile. "Quantification of Diastolic Viscoelastic Properties of Isolated Cardiac Muscle Cells". W ASME 2001 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2001. http://dx.doi.org/10.1115/imece2001/bed-23158.
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Abstract Pathological processes which cause diastolic congestive heart failure (CHF), such as pressure overload hypertrophy (POH), produce abnormalities in the material properties of cardiac muscle cells (cardiomyocytes) and may selectively alter its elastic stiffness, viscosity, or both. Previous methods used to characterize these cardiomyocyte viscoelastic properties were constrained by specific biological and engineering limitations, which prevented testing in conditions that mimic normal physiology. The current study proposes an uniaxial variable-rate stretching method, in which isolated cardiomyocytes embedded in a three-dimensional gel matrix were subjected to stretch. Physiological Ca++ (2.5 mM) and rapid stretch rates up to 100 μm/sec provided experimental conditions parallel to in vivo physiology. The proposed method identified and individually quantified both cellular stiffness and viscosity, and showed that POH increased both elastic and viscous cardiomyocyte diastolic properties.
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Agouni, Abdelali, Duck Y. Lee, Assaad A. Eid, Yves Gorin i Kumar Sharma. "The Protective Role of Sestrin2 in High Fat Diet-Induced Nephropathy". W Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2020. http://dx.doi.org/10.29117/quarfe.2020.0134.
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Introduction: Obesity is a major risk factor for type-2 diabetes predisposing patients to diabetic nephropathy (DN), the leading cause of end-stage renal failure. Glomerular injury is a prominent pathological feature of DN. Sestrin2 (Sesn2) is a stress-induced protein, but its role in DN has not been investigated. Therefore, we have determined the impact of Sesn2 deletion in a mouse model of obesityinduced nephropathy. Materials and methods: We examined the effects of Sesn2-deficiency in a longterm (22 weeks) mouse model of high fat diet (HFD)-induced obesity on glomerular structure. The severity of renal injury and fibrosis in wild type (Sesn2+/+) mice (fed HFD or chow diets) was compared to that in Sesn2-deficient mice (Sesn2-/- ) fed HFD or chow diets. Animal work was carried out under an IACUC-approved protocol. Results: Data showed that Sesn2 ablation exacerbated HFD-induced glomerular fibrotic injury as evidenced by mesangial matrix hypertrophy and accumulation of both fibronectin and collagen IV. Western blot analysis revealed that HFD- or chow-fed Sesn2-/- mice exhibited higher protein expression of key lipogenic enzymes, fatty acid translocase CD36 (an indicator of lipid uptake), fatty acid synthase and ATP citrate lyase. Sesn2-deficiency in obese mice resulted in podocyte loss as indicated by reduced expression of synaptopodin. Glomerular lesions like those observed in HFD-fed wild-type mice were detected in Sesn2-/-mice fed a chow diet, indicating that the basal deletion of Sesn2 is deleterious by itself. Conclusions: We provide the first evidence that Sesn2 is renoprotective in obesity-induced nephropathy by diminishing lipid accumulation and blocking excessive lipid uptake and de novo lipid synthesis. Understanding the protective of Sesn2 should yield novel therapeutic interventions to effectively preserve glomerular function in obesity and diabetes.
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Rizzuto, E., A. Musarò, A. Catizone i Z. Del Prete. "Morpho-Functional Interaction Between Muscle and Tendon in Hypertrophic MLC/mIGF-1 Mice". W ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19332.
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Tendons and ligaments are uniaxial viscoelastic connective tissues and, during normal activity, tendons transmit forces from muscles to bones, while ligaments stabilize the joints. Many experiments have been carried out to study ligaments and tendons mechanical properties [1], and the effects of training protocols [2] or specific pathologies. Recently, different transgenic mice models have been proposed as a new way to study in depth tendons’ function and development [3]. Within this context, we made use of pathological and transgenic animal models to investigate the morpho-functional interaction between muscles with an altered functionality and their tendons. In a previous work, by using the animal model of human Duchenne dystrophy, mdx, we found out that tendons connected to muscles with functional defects present reduced mechanical properties and an altered balance between alive and dead cells [4]. Here, we evaluated whether hypertrophic muscles would also involve alterations in tendon biomechanical properties. To do this, we used the transgenic animal model MLC/mIgf-1, were the local form of Igf-1 is over-expressed under a muscle specific promoter [5] inducing an increase in skeletal muscle mass and a proportional increment of force. To determine tendons’ elastic and viscous response separately, complex compliance has been computed with a new experimental method [6] which uses a pseudorandom Gaussian noise (PGN) to stimulate all the frequencies of interest within its bandwidth. Elasticity determines the tissue response to loading while viscous dissipation affects the likelihood of injuries to tendons. Indeed, knowing tendinous tissue viscoelasticity is central to better understand the mechanism between energy dissipation and tissue injuries. Finally, the hypothesis that changes in tendons’ mechanical properties could be correlated with alterations in the balance between alive and dead cells has been tested with an in situ cellular analysis.