The effect of statins on mRNA levels of genes related to inflammation, coagulation, and vascular constriction in HUVEC. Human umbilical vein endothelial cells.
Large-scale clinical trials have demonstrated significant reductions in cardiovascular events following statin therapy. The observed benefit of statin therapy, however, may be greater in these trials than is to be expected from lowering lipid levels alone. In order to clarify the mechanism by which statins prevent cardiovascular events in vascular wall cells, we investigated the changes in gene expression profiles after incubation with atorvastatin or pitavastatin in cultured human umbilical vein endothelial cells using DNA microarrays. Statins affected the expression levels of genes involved in inflammation, coagulation, and vascular constriction. The mRNA levels for interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) decreased after statin treatment. Statins reduced mRNA levels of plasminogen activator inhibitor-1 (PAI-1) and increased the mRNA levels of thrombomodulin. Statins reduced the mRNA levels of endothelin-1 and increased the mRNA levels of nitric oxide synthase-3 (eNOS). These results show that, statins are clinically effective because of their ability to change the gene expression profile of endothelial cells thereby preventing vascular events.
Morikawa
Shigeru
S
Department of Molecular Biology, Research Center for Advanced Science and Technology, University of Tokyo, Meguro, Tokyo, Japan.
Takabe
Wakako
W
Mataki
Chikage
C
Kanke
Toru
T
Itoh
Takahiro
T
Wada
Youichiro
Y
Izumi
Akashi
A
Saito
Yasushi
Y
Hamakubo
Takao
T
Kodama
Tatsuhiko
T
D000069059:Atorvastatin; D001777:Blood Coagulation / Q000235:genetics; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011758:Pyrroles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics; D014661:Vasoconstriction / Q000235:genetics
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D011804:Quinolines; D012333:RNA, Messenger; D011973:Receptors, LDL; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases; C108475:pitavastatin