Li Xiaohong, Xu Biao
Department of Cardiology, Clinical Drum Tower Hospital, Nanjing Medical University, Nanjing, 210008, China.
Appl Biochem Biotechnol. 2009 Jun;157(3):545-53. doi: 10.1007/s12010-008-8263-7. Epub 2008 Jun 18.
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.
羟甲基戊二酸单酰辅酶A还原酶抑制剂（他汀类药物）具有多效性。我们研究了辛伐他汀对外周血内皮祖细胞（EPCs）的作用及机制。大鼠在心肌梗死手术后分为辛伐他汀组和对照组。辛伐他汀治疗显著增加外周血CD34+CD133+细胞数量，体内血管内皮生长因子（VEGF）和AKT的血清浓度显著升高。在培养的EPC中，辛伐他汀增加了VEGF、AKT和eNOS的浓度。蛋白质印迹分析表明，辛伐他汀增加了eNOS和FKHRL1的磷酸化，而这可被PI3K/AKT途径阻滞剂LY294002阻断。我们的研究表明，辛伐他汀可增加心肌梗死后EPCs的动员。在体外研究中，辛伐他汀通过PI3K/AKT信号通路增加eNOS和FKHRL1的磷酸化。
