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Systems biology analysis unravels complementary action of combined Rosuvastatin and Ezetimibe therapy

ABSTRACT: Transcriptomics analysis to understand both efficacy and side effects of a cholesterol lowering drug combination therapy based on biological pathways and molecular processes affected by each drug alone or in combination. We have treated ApoE*3Leiden mice, a humanized atherosclerosis model with a unique human-like response to cholesterol-lowering drugs, with RSV and EZE alone and in combination. We demonstrate that processes affected by monotherapy can be retained and enhanced by combination therapy. In addition, combination therapy also affects a number of processes which are not predictable on basis of monotherapy – at least when analysis is performed within the borders of statistical significance. Our data however provide clues for these “non-predictable” effects.

ORGANISM(S): Mus musculus

PROVIDER: GSE38688 | GEO | 2013/02/27

SECONDARY ACCESSION(S): PRJNA168440

REPOSITORIES: GEO

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Systems biology analysis unravels complementary action of combined Rosuvastatin and Ezetimibe therapy

Project description:Transcriptomics analysis to understand both efficacy and side effects of a cholesterol lowering drug combination therapy based on biological pathways and molecular processes affected by each drug alone or in combination. We have treated ApoE*3Leiden mice, a humanized atherosclerosis model with a unique human-like response to cholesterol-lowering drugs, with RSV and EZE alone and in combination. We demonstrate that processes affected by monotherapy can be retained and enhanced by combination therapy. In addition, combination therapy also affects a number of processes which are not predictable on basis of monotherapy M-bM-^@M-^S at least when analysis is performed within the borders of statistical significance. Our data however provide clues for these M-bM-^@M-^\non-predictableM-bM-^@M-^] effects. Total RNA obtained from mouse liver from mice treated with High-Cholesterol (HC) diet as control (n=8) or HC+RSV (n=8) or HC+EZE (n=8) or HC+RSV+EZE (n=8).

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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

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Effect of Rosuvastatin on the Lipoprotein Proteome

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2012-01-11 | E-GEOD-34945 | biostudies-arrayexpress

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