Effects of simvastatin on vascular smooth muscle cells regulated by steroi regulatory element binding proteins / 上海第二医科大学学报

ABSTRACT

Objective To explore the biphasic effects of simvastatin on vascular smooth muscle cells(VSMCs),which were regulated by sterol regulatory element binding proteins(SREBPs).Methods①Rat primary VSMCs were cultured,the effects of different concentrations of simvastatin on proliferation and migration of VSMCs were observed,and the expression of SREBP-1 and SREBP-2 mRNA on VSMCs was detected.②Rat models of atherosclerosis were established,and were divided into atherosclerotic injured group(n =6),low concentration simvastatin group(n=6) and high concentration simvastatin group(n=6).Besides,normal control group(sham operation group,n=8) was established.Intragastric administration of simvastation of 0.5 mg?kg~(-1)?d~(-1) and 2.5 mg?kg~(-1)?d~(-1) was conducted in low concentration simvastatin group and high concentration simvastation group,respectively,while those in normal control group and atherosclerotic injured group were given same amount of normal saline.Rats were sacrificed 4 weeks later.Plasma lipid levels were examined by enzymic method,ratios of intima/(intima+tunica media) of thoracic aorta and left common carotid artery were determined,and the expression of SREBP-1 and SREBP-2 mRNA on blood vessels was detected by RT-PCR.Results Simvastatin didn't show biphasic effects on the proliferation and migration of VSMCs.Low concentration simvastatin didn't promote the proliferation and migration of VSMCs,while high concentration simvastatin showed inhibition effect on the proliferation and migration of VSMCs,which was dose-dependent and independent of lipid regulation effect by simvastatin. Simvastatin could activate the expression of SREBP-1 and SREBP-2 mRNA of VSMCs.Moreover,high concentration simvastatin could significantly activate the expression of SREBP-1 and SREBP-2 mRNA.Conclusion Simvastatin can inhibit the proliferation and migration of VSMCs by activating SREBPs.