The proangiogenic effect of simvastatin on experimental myocardial infarction of rats

Objective To investigate the roles of angiopoietin-1(Ang-1) and endothelial nitric oxide synthase(eNOS) in pro-angiogenic effect of simvastatin after experimental acute myocardial infarction(AMI).Methods Sixty healthy adult SD rats were randomly divided into the sham operated group、control group、simvastatin group、simvastatin plus L-NAME(inhibitor of NOS)group and simvastatin plus AMG386(inhibitor of Ang-1)group;Left anterior descending coronary underwent permanent occlusion to establish the AMI model.Rats with AMI were administered simvastatin[1 mg/(kg·d)],simvastatin plus L-NAME[40 mg/(kg·d)]and simvastatin plus AMG386[10 mg/(kg·wk)] respectively for 2 weeks.New microvessels in the ischemic area near the infarction myocardium were stained by CD31 and the density of new microvessels was dedected;Ang-1,eNOS and phosphoralated endothelial nitric oxide synthase at Ser1177(p-eNOS)were evaluated by Western blot and RT-PCR assay.Results(1)Simvastatin significantly increased the density of new microvessels(P0.05),but L-NAME and AMG386 siglificantly inhibited the proangiogenic effect of simvastatin(P0.05).(2)Simvastatin significantly improved the expression of Ang-1,eNOS andp-eNOS(P0.05),and AMG386 significantly decreased simvastatin induced upregulation of p-eNOS.ConclusionThe proangiogenic effect of simvastatin is associated with increased expression of Ang-1,eNOS and p-eNOS,and phosphoralation of eNOS maybe the downstream pathway for Ang-1 induced angiogenesis.