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Basic science: Cardiovascular disease basic research
e0044 The role of Ang1 and eNOS in the proangiogenic effect of simvastatin after myocardial infarction in rats
  1. He Quan,
  2. Qin Shu,
  3. Ma Kanghua,
  4. Luo Suxin,
  5. Zhang Xiaogang
  1. The First Affiliated Hospital Chongqing Medical University

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 was undergone 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 ischaemic 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 significantly inhibited the pro-angiogenic 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 pro-angiogenic 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.

  • Simvastatin
  • acute myocardial infarction
  • angiogenesis
  • angiopoietin-1
  • endothelial nitric oxide synthase

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