In-vivo effects of simvastatin and rosuvastatin on global gene expression in peripheral blood leucocytes in a human inflammation model

Pharmacogenetics and Genomics
Wolfgang M SchmidtMarkus Müller

Abstract

To gain insight into molecular mechanisms of anti-inflammatory effects of statins, we have studied global gene expression in circulating leucocytes in an in-vivo model of acute inflammation following statin administration. For this purpose, a randomized, double-blind, placebo-controlled, crossover study was conducted in six healthy male volunteers, who received simvastatin (80 mg/day), rosuvastatin (40 mg/day) or placebo before infusion of E. coli lipopolysaccharide (LPS). Leucocyte RNA isolated before and after statin treatment, and after LPS-infusion was subjected to GeneChip transcript profiling (n=42). Data analysis revealed that statins exert little effect on leucocyte gene expression. Statin-responsive genes included several immune response genes and the cholesterol efflux transporter (ABCA1). Rosuvastatin appeared to moderately downregulate expression of the genes encoding the inflammatory response proteins orosomucoid (ORM1) and interleukin 18 receptor accessory protein (IL18RAP). LPS-infusion induced a pronounced response of the leucocyte transcriptome, notably affecting transcripts related to immune regulation, cell proliferation and motility. While the majority of LPS-induced changes were not modulated by either stat...Continue Reading

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