Qiliqiangxin ameliorates cardiac dysfunction in heart failure rats post myocardial infarction via activation of HIF / VEGF pathway

Abstract: Objective: To evaluate the effects of superfine Qiliqiangxin powder (QL) on cardiac function and microan- giogenesis in heart failure (HF) rats post myocardial infarction, and to explore the related mechanisms. Methods: Myocardial infarction was induced by ligation of the left anterior descending coronary artery in male Sprague-Dawley (SD) rats. Two weeks after MI, rats with a left ventricular ejection fraction < 50% were divided into HF+NS (saline, orally) group, HF+QL (0.6 g/kg/day, via intragastric administration) group and HF+QL (0.6 g/kg/day, via intragastric administration)+HIF (2-MeOE2, HIF-1α inhibitor, 1 mmol/kg/week, via intraperitoneal injection) group, respectively, rats in sham group underwent similar surgical procedure without coronary ligation (n=6 for each group). Six weeks later, cardiac structure and function were examined by echocardiography, microangiogenesis was assessed by im- munostaining CD31, and myocardial protein and mRNA express ions of p53, HIF-1α and VEGF were determined by Western blotting and RT-PCR, respectively. Results: Compared with sham group rats, heart failure rats exhibited enlarged cardiac chamber, reduced left ventricular ejection fraction and rare microvascular density (all p < 0.05). QL treatment ameliorated cardiac remodeling, improved cardiac function and promoted microangiogenesis around infarct border zone. Moreover, myocardial p53 expression downregulated and HIF-1α and VEGF expressions up- regulated post QL treatment, above beneficial effects were partly counteracted by cotreatment with HIF-1α inhibi- tor 2-MeOE2. Conclusions: Our results showed that QL treatment could significantly improve cardiac function and enhance microangiogenesis in HF rats post myocardial infarction via modulating HIF-1α/VEGF pathway.