Abstract: Objective To investigate the roles of angiopoietin-1(Ang-1) and endothelial nitric oxide synthase(eNOS) in pro-angiogenic effect of simvastatin after experimental myocardial infarction(MI). Methods 60 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 MI model. Rats with MI 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 blotting and RT-PCR assay. Results (1) simvastatin significantly increased the density of new microvessels(P<0.05),but L-NAME and AMG386 siglificantly inhibited the proangiogenic effect of simvastatin (P<0.05).(2) simvastatin significantly improved The expression of Ang-1、eNOS and p-eNOS (P<0.05), and AMG386 significantly decreased simvastatin induced upregulation of p-eNOS. Conclusion The 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.

Key words: simvastatin, acute myocardial infarction, angiogenesis, angiopoietin-1, endothelial nitric oxide synthase