title: Global analysis of RNA expression profile in human vascular cells treated with statins.
abstract: In addition to a lipid-lowering effect, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have an effect on the expression levels of many genes. In order to elucidate the range of this effect as comprehensively as possible, we investigated the changes in gene expression profiles brought about by atorvastatin or pitavastatin in cultured human umbilical vein endothelial cells (HUVEC), cultured human coronary artery smooth muscle cells (HCASMC) and cultured human hepatocarcinoma Hep G2 cells by means of DNA microarrays. Among the 6146 genes in the array, statins affected the expression levels of genes involved in coagulation, vascular constriction and cell growth in a cell-type specific manner. In HUVEC, they induced integrin beta4 and thrombomodulin profoundly, and profoundly suppressed pentraxin 3 both at 8 and 24 hours. In HCASMC, the statins induced thrombomodulin and urokinase inhibitor, and potently suppressed the cysteine-rich angiogenic inducer 61 and cyclin B. Many genes related to the cell cycle and/or growth were also regulated in HUVEC and HCASMC by the statins. These results indicate that many aspects of the pleiotropic effect can be mediated by transcriptional control by statins. Genes newly identified by this study may be useful in statin therapy.
authors.affiliation: Laboratory for Systems Biology and Medicine, RCAST, University of Tokyo, #35, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morikawa
authors.forename: Wakako
authors.initials: W
authors.lastname: Takabe
authors.forename: Chikage
authors.initials: C
authors.lastname: Mataki
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Akashi
authors.initials: A
authors.lastname: Izumi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012313:RNA