Effect of Simvastatin on endothelial cells
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ABSTRACT:
PROVIDER: PRJNA877683 | ENA |
REPOSITORIES: ENA
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Project description:Effect of Simvastatin on endothelial cells (heart ATAC-seq)
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Project description:Effect of Simvastatin on endothelial cells (iEC ATAC-seq)
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Project description:We report that simvastatin induces an immunoregulatory transcriptional profile in endothelial cells that is potent to modulate CD4+ T cell biology.
2021-10-28 | GSE171123 | GEO
Project description:Transcriptomic profiling of simvastatin-treated human umbilical vein endothelial cells
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Project description:The aim of our study was to assess the impact of simvastatin on the amount of cytosolic lipid droplets (LDs), which are implicated in many biological processes including proliferation, inflammation, carcinogenesis, apoptosis, necrosis or growth arrest. Human pancreatic cancer cells MiaPaCa-2 were treated with simvastatin (6 and 12 _M) for 24 hours. Changes in expression of genes related to lipid metabolism in the simvastatin-treated cells were examined by DNA microarray analysis. The treatment of the cells with simvastatin increased their intracellular content of LDs, partially due to the uptake of cholesterol and triacylglycerides from medium; but in particular, due to enhanced synthesis of triacylglycerides as proved by detection of significant overexpression of genes related to de novo synthesis of triacylglycerides and phospholipids. Further, simvastatin markedly influenced expression of genes directly affecting cell proliferation and signaling.
2013-11-21 | E-MTAB-1501 | biostudies-arrayexpress
Project description:Background Simvastatin modulates numerous stem cell functions, including stemness maintenance and differentiation. The present study aimed to explore the effect of simvastatin on the osteogenic differentiation of SCAPs in vitro. Methods Cells were isolated from apical papilla, and mesenchymal stem cell features were characterised. Cells were treated with various concentrations of simvastatin (100-1,000 nM). The mRNA expression profile of simvastatin-treated SCAPs was examined using RNA sequencing technique. The osteogenic differentiation abilities were assessed. Alkaline phosphatase activity was determined. The mineralisation was visualised using Alizarin Red S and Von Kossa staining. The osteogenic marker gene expression was determined using a quantitative polymerase chain reaction. Results RNA sequencing data demonstrated that simvastatin upregulated genes enriched in those pathways involving osteogenic differentiation, including the TGF-beta signalling pathway, FoxO signalling pathway, and MAPK signalling pathway, while the downregulated genes were involved in pathways related to cell proliferation and apoptosis, for example, DNA replication, cell cycle, and p53 signalling pathway. Simvastatin promoted mineral deposition in a dose-dependent manner, corresponding with the upregulation of osteogenic marker genes namely OSX, DMP1, DSPP, and OCN. Pretreatment with TGF-beta receptor inhibitor, SB431542, resulted in a moderately attenuated effect on simvastatin-induced mineralisation and osteogenic marker gene expression. Conclusions Simvastatin enhances osteogenic differentiation in SCAPs, potentially via TGF-beta signalling, implicating its potential role as an adjunctive molecule in dental pulp healing and regeneration in vital pulp treatment approaches.
2025-01-22 | GSE286540 | GEO
Project description:Statins, a class of hydroxy-methylglutaryl-coenzyme A reductase inhibitors that repress the mevalonate pathway, have been increasingly recognized to reduce cardiovascular risks in a pleiotropic manner independent of their lipid-lowering effects. Yet, the precise molecular mechanisms underlying their cardiovascular protection effects remain elusive. As an unlimited alternate source of human primary cells, we sought to use human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) to tackle this question. We treated iPSC-ECs with or without statins in both baseline and diabetic conditions, and evaluated their biological functions specifically at the transcriptional and epigenetic levels using an array of state-of-the-art technologies, such as transcriptome profiling, chromatin immunoprecipitation sequencing (ChIP-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), CRISPR knockout and CRISPR interference (CRISPRi). Furthermore, we validated our in vitro findings of the endothelial protective role of statin using a diabetic mouse model. We observed that, compared to vehicles, statins significantly improved endothelial functions in both baseline and diabetic conditions in iPSC-ECs. Mechanistically, statins could reduce chromatin accessibility at TEAD elements and ultimately at endothelial-to-mesenchymal transition (EndMT)-regulating genes in a yes-associated protein (YAP)-dependent manner. Interestingly, inhibition of geranylgeranyltransferase I (GGTase I), a mevalonate pathway intermediate, was able to block YAP nuclear translocation and thereby YAP activity by suppressing RhoA signaling. We also identified a direct target of statin-YAP signaling, a novel enhancer of SOX9 gene, which plays a critical role in EndMT process. Based on these observations, we further confirmed that inhibition of any component of the GGTase-RhoA-YAP-SOX9 signaling axis using either genetic or pharmacological approaches was effective to rescue EndMT-associated endothelial dysfunction both in vitro and in vivo, especially under diabetic conditions.
2025-09-07 | GSE212879 | GEO
Project description:Statins, a class of hydroxy-methylglutaryl-coenzyme A reductase inhibitors that repress the mevalonate pathway, have been increasingly recognized to reduce cardiovascular risks in a pleiotropic manner independent of their lipid-lowering effects. Yet, the precise molecular mechanisms underlying their cardiovascular protection effects remain elusive. As an unlimited alternate source of human primary cells, we sought to use human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) to tackle this question. We treated iPSC-ECs with or without statins in both baseline and diabetic conditions, and evaluated their biological functions specifically at the transcriptional and epigenetic levels using an array of state-of-the-art technologies, such as transcriptome profiling, chromatin immunoprecipitation sequencing (ChIP-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), CRISPR knockout and CRISPR interference (CRISPRi). Furthermore, we validated our in vitro findings of the endothelial protective role of statin using a diabetic mouse model. We observed that, compared to vehicles, statins significantly improved endothelial functions in both baseline and diabetic conditions in iPSC-ECs. Mechanistically, statins could reduce chromatin accessibility at TEAD elements and ultimately at endothelial-to-mesenchymal transition (EndMT)-regulating genes in a yes-associated protein (YAP)-dependent manner. Interestingly, inhibition of geranylgeranyltransferase I (GGTase I), a mevalonate pathway intermediate, was able to block YAP nuclear translocation and thereby YAP activity by suppressing RhoA signaling. We also identified a direct target of statin-YAP signaling, a novel enhancer of SOX9 gene, which plays a critical role in EndMT process. Based on these observations, we further confirmed that inhibition of any component of the GGTase-RhoA-YAP-SOX9 signaling axis using either genetic or pharmacological approaches was effective to rescue EndMT-associated endothelial dysfunction both in vitro and in vivo, especially under diabetic conditions.
2025-09-07 | GSE212878 | GEO
Project description:HMG-CoA reductase inhibitors, statins, have beneficial vascular effects beyond their cholesterol-lowering action. These pleiotropic effects include an anti-inflammatory effect on macrophages. Since macrophages play a central role in atherogenesis, we further characterized the effects on peripheral blood monocyte-macrophages (HPBM). Using Affymetrix gene chip analysis of simvastatin-treated HPBM, we found that simvastatin treatment lead to the downregulation of the expression of many proinflammatory genes including several chemokines (e.g. MCP-1, MIP-1 alpha and β, RANTES, several other CC and CXC chemokines, IL-2 receptor-β, and leukemia inhibitory factor), members of the tumor necrosis factor family (e.g. lymphotoxin beta and TRAIL), VCAM-1, ICAM-3, and tissue factor (TF). Simvastatin also modulated the expression of several transcription factors essential for the inflammatory response: simvastatin downregulated the expression of NF-kappaB relA/p65 subunit and ets-1 transcription factor, and upregulated the expression of a novel atheroprotective transcription factor, Kruppel-like factor 2 (KLF-2). The effects of simvastatin on KLF-2 and its target genes were dependent on protein prenylation, since inhibitors of protein prenylation had a similar inhibitory effect in THP-1 derived macrophages. Additionally, by lentiviral overexpression KLF-2 we showed that the effect of simvastatin on MCP-1 and TF were dependent on KLF-2. We concluded that simvastatin had a strong anti-inflammatory effect on macrophages, which includes upregulation of the atheroprotective transcription factor KLF-2. These findings further explain the beneficial pleiotropic effects of statins on cardiovascular diseases. Keywords: time-course, response to treatment
2006-12-31 | GSE4883 | GEO
Project description:Statins protect against the development of atherosclerosis via cholesterol-dependent and –independent mechanisms. Understanding the molecular mechanisms mediating simvastatin induced atheroprotective effects is critical for designing anti-atherosclerotic agents. Here, we showed that simvastatin decreases the expression of the Polycomb methyltransferase EZH2 in endothelial cells. To better understand the influence of the simvastatin-induced EZH2 downregulation on endothelial transcriptome, we performed RNA-sequencing study to evaluate differential gene expression after overexpression of EZH2 in the presence of simvastatin treatment. We found simvastatin treatment altered a subset of genes that can be rescued with EZH2 overexpression. Therefore, simvastatin treated endothelial cells display an atheroprotective phenotype by downregulating EZH2.
2017-08-18 | GSE85799 | GEO