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Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome [Affymetrix platform]

ABSTRACT: With particular emphasis on interactions between cholesterol homeostasis and drug metabolism we investigate the transcriptome of human primary hepatocytes treated by two commonly prescribed cholesterol lowering drugs atorvastatin and rosuvastatin and by rifampicin that serves as an outgroup as well as a model substance for induction of nuclear receptor PXR. Expression profiling with Affymetrix whole genome arrays shows that statins induce extensive transcriptome changes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE24187 | GEO | 2011/09/05

SECONDARY ACCESSION(S): PRJNA133701

REPOSITORIES: GEO

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Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome [Affymetrix platform]

Project description:With particular emphasis on interactions between cholesterol homeostasis and drug metabolism we investigate the transcriptome of human primary hepatocytes treated by two commonly prescribed cholesterol lowering drugs atorvastatin and rosuvastatin and by rifampicin that serves as an outgroup as well as a model substance for induction of nuclear receptor PXR. Expression profiling with Affymetrix whole genome arrays shows that statins induce extensive transcriptome changes. 7 condition experiment: 3 treatments (atorvastatin, rifampicin, rosuvastatin), each measured at 2 time points (24 and 48 hours), and untreated cells. 4-6 biological replicates for each condition.

2011-09-04 | E-GEOD-24187 | biostudies-arrayexpress

Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome [Steroltalk platform]

2011-09-05 | GSE24186 | GEO

Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome [Steroltalk platform]

Project description:With particular emphasis on interactions between cholesterol homeostasis and drug metabolism we investigate the transcriptome of human primary hepatocytes treated by two commonly prescribed cholesterol lowering drugs atorvastatin and rosuvastatin and by rifampicin that serves as an outgroup as well as a model substance for induction of nuclear receptor PXR. Expression profiling with dedicated Steroltalk cDNA arrays shows that statins induce extensive transcriptome changes. 10 condition experiment: 3 treatments (atorvastatin, rifampicin, rosuvastatin), each measured at 3 time points (12, 24 and 48 hours), and untreated cells. 3-7 biological replicates for each treatment condition, 20 biological and technical replicates for untreated cells. Common reference design.

2011-09-04 | E-GEOD-24186 | biostudies-arrayexpress

Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome

Project description:This SuperSeries is composed of the following subset Series: GSE24186: Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome [Steroltalk platform] GSE24187: Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome [Affymetrix platform] Refer to individual Series

2011-09-04 | E-GEOD-24188 | biostudies-arrayexpress

Effect of rosuvastatin and atorvastatin in combination with high-cholesterol diet on cholesterol homeostasis

Project description:The aim of the study was to see any effect of rosuvastatina or atorvastatin on cholesterol homeostasis after 24 hours in C57BL/6 hyperlipidemic mice (induced by diet). Experiments were perfomed using a custom Steroltalk v2 microarray. Effect of both statins on drug metabolism was also evaluated. All experiments were done within the European sixth Framework program âSteroltalkâ (www.steroltalk.net). Animals were given one peroral application of vehicle (tap water), 20 mg/kg rosuvastatin or 40 mg/kg atorvastatin after one week of 1% cholesterol diet. After 24h they were sacrificed and total RNA was isolated from the livers. Each sample was hybridized with a reference sample to Steroltalk v2 microarrays.

2010-06-19 | E-GEOD-13689 | biostudies-arrayexpress

Effect of rosuvastatin and atorvastatin in combination with high-cholesterol diet on cholesterol homeostasis

2009-11-20 | GSE13689 | GEO

Effect of TCPOBOP, PCN, rosuvastatin, and atorvastatinin on cholesterol homeostasis

Project description:This SuperSeries is composed of the following subset Series: GSE13688: Effect of TCPOBOP and PCN in combination with high-cholesterol diet on genes involved in cholesterol homeostasis GSE13689: Effect of rosuvastatin and atorvastatin in combination with high-cholesterol diet on cholesterol homeostasis Refer to individual Series

2010-10-08 | E-GEOD-13721 | biostudies-arrayexpress

Therapeutic effects of Rosuvastatin in hypercholesterolemic prediabetic mice in the absence of low density lipoprotein receptor

Project description:Statins are efficient in preventing cardiovascular disease progression, but their effects in the absence of low density lipoprotein receptor (LDLR) and on the risk of diabetes are not yet well characterized. The aim was to clarify systemic and pleiotropic effects of Rosuvastatin on cardiovascular and diabetic phenotypes in hypercholesterolemic prediabetic mice. The IGF-II/LDLR-/-ApoB100/100 animals were tested for Rosuvastatin effects on plasma glucose, insulin, lipids, atherosclerosis and liver steatosis. To achieve a more comprehensive view, genes differentially expressed in response to Rosuvastatin were identified by RNA sequencing in liver tissue. Rosuvastatin significantly reduced plasma cholesterol in hypercholesterolemic LDLR – deficient mice, but had no effects on atherosclerosis development at aortic sinus level and in coronary arteries. Rosuvastatin also significantly reduced liver steatosis without any pronounced effects on glucose or insulin levels. RNA sequencing revealed that Rosuvastatin – responsive hepatic genes are involved in cholesterol metabolism and in anti-inflammatory response. In addition, significant changes were detected in the expression of Perilipin 4 and 5 which are involved in lipid droplet formation in the liver. For the first time it was shown that Tribbles proteins are affected by Rosuvastatin treatment in the hypercholesterolemic mice. In conclusion, Rosuvastatin treatment had several positive effects in hypercholesterolemic mice showing early signs of diabetes, and many of these outcomes are unrelated to direct effects on cholesterol and lipoprotein metabolism. These results increase our understanding about the systemic and pleiotropic effects of Rosuvastatin in the absence of LDLR expression.

2018-11-23 | GSE111125 | GEO

Transcriptomic profiling of differentially expressed mRNA, lncRNA and circRNA in atorvastatin-treated human endothelial cells

Project description:Statins are competitive inhibitors of (3-hydroxy-3-methylglutaryl coenzyme A) HMG-CoA reductase. The primary mechanism of statins is the lowering of serum cholesterol through inhibiting hepatic cholesterol biosynthesis. Statins exert pleiotropic vasoprotective and atheroprotective effects in the vasculature, with its mechanism of action being incompletely understood.To depict the statin-regulated mRNA,long non-coding RNA (lncRNA) and circular RNA (circRNA) in human endothelial cells, we performed transcriptomic profiling of human umbilical vein endothelial cells (HUVECs) with atorvastatin treatment.Differentially expressed mRNA, lncRNA and circRNA may represent novel therapeutic targets against cardiovascular diseases.

2023-05-31 | GSE176531 | GEO

Effect of Rosuvastatin on the Lipoprotein Proteome

Project description:Statins lower plasma cholesterol by as much as 50%, thus reducing future cardiovascular events. However, the physiological effects of statins are diverse and not all are related to LDL-C lowering. We performed a small clinical pilot study to assess the impact of statins on lipoprotein-associated proteins in healthy individuals (n=10) with normal LDL-C (<130 mg/dL), who were treated with rosuvastatin (20 mg/day) for 28 days. Proteomic analysis of size-exclusion chromatography isolated LDL, HDL-L (large) and HDL-S (small) fractions and spectral counting was used to compare relative protein detection before and after statin therapy. Significant protein changes were found in each lipoprotein pool and included both increases and decreases in several proteins involved in lipoprotein metabolism, complement regulation and acute phase response. The most dramatic effect of the rosuvastatin treatment was an increase in alpha-1-antirypsin (A1AT) spectral counts associated with HDL-L particles. Quantitative measurement by ELISA confirmed an average 5.7-fold increase in HDL-L associated A1AT. Molecular modeling predictions indicated that the hydrophobic reactive center loop of A1AT, the functional domain responsible for its protease inhibitor activity, is likely involved in its lipid binding and its association with HDL was found to protect A1AT against oxidative inactivation. Cell culture experiments, using J774 macrophages, demonstrated that the association of A1AT with HDL enhances its anti-protease activity, preventing elastase induced production of tumor necrosis factor alpha. In conclusion, we show that statins can significantly alter the protein composition of both LDL and HDL and our studies reveal a novel functional relationship between A1AT and HDL. The upregulation of A1AT on HDL enhances its anti-inflammatory functionality, which may contribute to the non-lipid lowering beneficial effects of statins.

2018-10-24 | PXD002633 | Pride

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