title: Comparative effects of statins on murine cardiac gene expression profiles in normal mice.
abstract: Recent clinical data suggest that the efficacy of statin treatment in patients with heart failure varies depending on the drugs administered. The present study was undertaken to compare murine cardiac gene expression profiles following treatment with four different statins. In normal male C57BL/6J mice, 4 weeks of treatment with or without a statin (pitavastatin, pravastatin, rosuvastatin, or atorvastatin) did not affect any biochemical parameters, including the lipid profile. However, cardiac gene expression profiling by microarray analysis revealed distinct patterns among the five groups. Several genes that might be involved in cardiac function, including Ccnd2, Klf7 and Timp3, were differentially regulated by treatment with a specific statin. In the primary cultured neonatal mouse cardiomyocytes, statin-induced changes in the expression of these genes were largely unaffected by supplementation with mevalonic acid. These data indicate that statins directly regulate cardiac gene expression in a drug-specific manner in normal mice. Additional studies are needed to determine whether these differences influence the clinical efficacy in particular patients, such as those with heart failure.
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kumazaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ando
authors.forename: Kentarou
authors.initials: K
authors.lastname: Ushijima
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D056742:Cyclin D2 / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008297:Male; D008798:Mevalonic Acid / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics
chemical_list: C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C426008:Klf7 protein, mouse; D051741:Kruppel-Like Transcription Factors; D019717:Tissue Inhibitor of Metalloproteinase-3; D008798:Mevalonic Acid