HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3'-kinase/AKT signal transduction pathway.
HMG-CoA reductase inhibitor (statins) are known to have pleiotropic effects. We examined the effect and mechanism of simvastatin on peripheral endothelial progenitor cells (EPCs). Rats were divided into simvastatin group and the control group after cardiac infarction operation. Simvastatin treatment significantly increased the number of peripheral blood CD34+ CD133+ cells, and serum concentration of vascular endothelial growth factor (VEGF) and AKT was markedly increased in vivo. In cultured EPC, simvastatin increased the concentrations of VEGF, AKT and eNOS. Western blots analysis showed that simvastatin increased the phosphorylation of eNOS and FKHRL1, which can be blocked by the PI3K/AKT pathway blocker LY294002 . Our study demonstrated that simvastatin increases the mobilization of EPCs after cardiac infarction. In in vitro study, simvastatin increases the phosphorylation of eNOS and of FKHRL1 through the PI3K/AKT signaling pathway.
Department of Cardiology, Clinical Drum Tower Hospital, Nanjing Medical University, Nanjing, 210008, China.
Xiaohong
X
Li
Biao
B
Xu
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D019821:Simvastatin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010455:Peptides; C000606025:Prom1 protein, rat; D042461:Vascular Endothelial Growth Factor A; D019821:Simvastatin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt