PTEN Deficiency Promotes Pathological Vascular Remodeling of Human Coronary Arteries
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ABSTRACT:
PROVIDER: PRJNA434117 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression profiles of Rat aortic smooth muscle clonal isolates of PTEN knock-down and control wild-type. We used Affymetrix microarrays to detail the global program of gene expression changes between PTEN deficient and wild type smooth muscle cells. We identified distinct classes of up- and down-regulated genes during this process.
2018-02-15 | GSE110622 | GEO
Project description:Phosphatase and tensin homolog (PTEN) is an essential regulator of the differentiated vascular smooth muscle cell (SMC) phenotype. Our goal was to establish that PTEN loss promotes SMC dedifferentiation and pathological vascular remodeling in human atherosclerotic coronary arteries and nonatherosclerotic coronary arteries exposed to continuous-flow left ventricular assist devices (CF-LVADs). Arteries were categorized as nonatherosclerotic hyperplasia (NAH), atherosclerotic hyperplasia (AH), or complex plaque (CP). NAH coronary arteries from CF-LVAD patients were compared to NAH coronaries from non-LVAD patients. Intimal PTEN and SMC contractile protein expression was reduced compared with the media in arteries with NAH, AH, or CP. Compared with NAH, PTEN and SMC contractile protein expression was reduced in the media and intima of arteries with AH and CP. NAH arteries from CF-LVAD patients showed marked vascular remodeling and reduced PTEN and α-smooth muscle actin (αSMA) in medial SMCs compared with arteries from non-LVAD patients; this correlated with increased medial collagen deposition. Mechanistically, compared with ApoE-/- mice, SMC-specific PTEN-null/ApoE-/- double-knockout mice exhibited accelerated atherosclerosis progression and increased vascular fibrosis. By microarray and validated quantitative RT-PCR analysis, SMC PTEN deficiency promotes a global upregulation of proinflammatory and profibrotic genes. We propose that PTEN is an antiinflammatory, antifibrotic target that functions to maintain SMC differentiation. SMC loss of PTEN results in pathological vascular remodeling of human arteries.
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Project description:Bare-metal (BMS) and drug-eluting stents (DES) were implanted in pig coronary arteries with an overstretch during coronary angioplasty under optical coherence tomography guidance. Arteries subjected to plain old balloon angioplasty (POBA) alone served as controls. Stented/balloon dilated segments were harvested 1, 3, 7, 14 and 28 days post-intervention for proteomics analysis. At day 28 all stented arteries showed a neointima formation covering the stent struts. The evolved neointima was separated from the media and analysed in a separate proteomics analysis. In total, 31 samples were analysed for the media by LC-MS/MS (n=3 BMS/DES at each time-point 1, 3, 7 and 28 days; n=4 POBA early [day1-day3] and n=3 POBA late [day 14 - day28]). For the neointima a total of 14 samples were analysed (n=7 BMS, n=7 DES at 28 days) including the neointima of arteries of a second cohort with 4 samples each for BMS and DES day 28. The neointima samples were run in duplicates.
2017-11-24 | PXD005726 | Pride
Project description:Atherosclerotic plaques tend to form in the major arteries at certain predictable locations. As these arteries vary in atherosusceptibility, inter-arterial differences in endothelial cell (EC) biology are of considerable interest. To explore the origin of differences observed between typical atheroprone and atheroresistant arteries, we used DNA microarrays to compare gene expression profiles of harvested porcine coronary (CECs) and iliac (IECs) artery ECs grown in static culture out to passage four. Fewer differences were observed between the transcriptional profiles of CECs and IECs in culture compared to in vivo, suggesting that most differences observed in vivo were due to distinct environmental cues in the two arteries. One-class significance of microarrays revealed that most in vivo interarterial differences disappeared in culture, as fold differences after passaging were not significant for 85% of genes identified as differentially expressed in vivo at a 5% false discovery rate. However, the three homeobox genes HOXA9, HOXA10, and HOXD3 remained under-expressed in coronary endothelium for all passages by at least 9, 8, and 2-fold, respectively. Continued differential expression despite removal from the in vivo environment suggests that primarily heritable or epigenetic mechanism(s) influence transcription of these three genes. Quantitative real-time polymerase chain reaction confirmed expression ratios for seven genes associated with atherogenesis and over- or under-expressed by 3-fold in CECs relative to IECs. The present study provides evidence that both local environment and vascular bed origin modulate gene expression in arterial endothelium. The transcriptional differences observed here may provide new insights into pathways responsible for coronary artery susceptibility. Endothelial cells were freshly harvested from right coronary and iliac arteries from four pigs. Cells were cultured out to passage four. RNA was isolated after each passage and expression profiles were obtained using oligo microarrays.
2010-12-18 | E-GEOD-19593 | biostudies-arrayexpress
Project description:Phenotypic heterogeneity among arterial ECs is particularly relevant to atherosclerosis since the disease occurs predominantly in major arteries, which vary in their atherosusceptibility. To explore EC heterogeneity, we used DNA microarrays to compare gene expression profiles of freshly harvested porcine coronary and iliac artery ECs. We demonstrate that in vivo the endothelial transcriptional profile of a coronary artery (the right coronary artery) is intrinsically different from that of a major conduit vessel (the external iliac artery), and that this difference is consistent with former vessel being more prone to atherosclerosis. Keywords: coronary atherosclerosis, endothelial heterogeneity, microarray, gene expression Endothelial cells were freshly harvest from right coronary, left and right iliac arteries from four pigs. RNA were isolated and expression profiles were obtained using olig microarrays.
2010-06-20 | E-GEOD-10938 | biostudies-arrayexpress
Project description:To understand the mechanism of coronary artery aneurysmal dilatation, we identified and compared the expression of circulating miRNAs in three groups of patients. Group 1 enrolled patients with aneurysmal dilatation of coronary arteries (n = 20), Group 2 included patients with angiographically confirmed coronary artery disease (CAD), whereas Group 3 included 20 patients with normal coronary arteries. The miRNAs were isolated from plasma and profiled using PCR arrays miRCURY LNA Serum/Plasma Focus PCR Panels. We demonstrated that the plasma miRNAs levels were significantly different in Group 1 in collation with Group 2 and Group 3 (fold change > 2 and p < 0.05). The comparison of Group 1 with Group 3 identified twenty-one significantly up-regulated and two down-regulated miRNAs in patients with aneurysmal coronary artery dilatation compared to the control groups. Moreover, we identified six up-regulated and two down-regulated miRNAs in patients with CAD compared to the controls. The third comparison revealed four up-regulated and three down-regulated miRNAs in Group 1, when compared to CAD patients. In conclusion, this study demonstrates the specific signature of plasma miRNA, namely up-regulated and down-regulated, in patients with abnormal dilatation of coronary arteries and the comparison between the groups consisting of atherosclerotic and control patients.
2022-03-18 | GSE198885 | GEO
Project description:Atherosclerotic plaques tend to form in the major arteries at certain predictable locations. As these arteries vary in atherosusceptibility, inter-arterial differences in endothelial cell (EC) biology are of considerable interest. To explore the origin of differences observed between typical atheroprone and atheroresistant arteries, we used DNA microarrays to compare gene expression profiles of harvested porcine coronary (CECs) and iliac (IECs) artery ECs grown in static culture out to passage four. Fewer differences were observed between the transcriptional profiles of CECs and IECs in culture compared to in vivo, suggesting that most differences observed in vivo were due to distinct environmental cues in the two arteries. One-class significance of microarrays revealed that most in vivo interarterial differences disappeared in culture, as fold differences after passaging were not significant for 85% of genes identified as differentially expressed in vivo at a 5% false discovery rate. However, the three homeobox genes HOXA9, HOXA10, and HOXD3 remained under-expressed in coronary endothelium for all passages by at least 9, 8, and 2-fold, respectively. Continued differential expression despite removal from the in vivo environment suggests that primarily heritable or epigenetic mechanism(s) influence transcription of these three genes. Quantitative real-time polymerase chain reaction confirmed expression ratios for seven genes associated with atherogenesis and over- or under-expressed by 3-fold in CECs relative to IECs. The present study provides evidence that both local environment and vascular bed origin modulate gene expression in arterial endothelium. The transcriptional differences observed here may provide new insights into pathways responsible for coronary artery susceptibility.
2010-12-18 | GSE19593 | GEO
Project description:Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. Vascular expression and activity of TNFa convertase enzyme were preserved in aging. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly.
2010-06-05 | E-GEOD-619 | biostudies-arrayexpress
Project description:Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. Vascular expression and activity of TNFa convertase enzyme were preserved in aging. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly. Keywords: repeat sample
2003-10-28 | GSE616 | GEO
Project description:Phenotypic heterogeneity among arterial ECs is particularly relevant to atherosclerosis since the disease occurs predominantly in major arteries, which vary in their atherosusceptibility. To explore EC heterogeneity, we used DNA microarrays to compare gene expression profiles of freshly harvested porcine coronary and iliac artery ECs. We demonstrate that in vivo the endothelial transcriptional profile of a coronary artery (the right coronary artery) is intrinsically different from that of a major conduit vessel (the external iliac artery), and that this difference is consistent with former vessel being more prone to atherosclerosis. Keywords: coronary atherosclerosis, endothelial heterogeneity, microarray, gene expression
2008-08-23 | GSE10938 | GEO