Danggui Buxue decoction promotes angiogenesis by up-regulation of VEGFR1/2 expressions and down-regulation of sVEGFR1/2 expression in myocardial infarction rat

Background: The traditional herbal compound Danggui Buxue decoction (DBD), has long been used for the prevention and treatment of cardiovascular diseases, however, the underlying molecular mechanism for its effect remains still unknown. So this study would to investigate the effect of DBD on cardiac damage induced by myocardial infarction (MI) challenge. Methods: SD Rats with ligation of left anterior descending (LAD) coronary artery were randomly divided into MI, MI plus Betaloc Zok, MI plus DBD high dose, and MI plus DBD low dose group, together with sham-operated group. After corresponding treatment for consecutive 4 weeks, cardiac function was evaluated by hemodynamics with the method of pressure-volume conduit system. Cardiac histological morphology, microvascular density and the expressions of VEGF and VEGFR1/2 mRNA and their relative protein including VEGF, membranous VEGFR1 (VEGFR1), soluble VEGFR1 (sVEGFR1), VEGFR2, and sVEGFR2 were examined by hematoxylin & eosin staining, immunohistochemical staining and quantitative polymerase chain reaction and western blot assay, respectively. Results: It showed that a significant impaired cardiac function and a remarkably inducible increase in fibrotic scar formation, microvascular density and VEGF mRNA expressions in MI rats. While DBD treatment could markedly boost cardiac angiogenesis further, hinder fibrotic scar formation, and improve declined cardiac function. Apart from the up-regulation of VEGF mRNA and VEGF and the down-regulation of sVEGFR1/2, high dose of DBD dedicated to increasing VEGFR1 mRNA and VEGFR1 expression, while low dose to elevating VEGFR2 mRNA and VEGFR2 expression. Conclusion: The present study demonstrated that DBD could accelerate cardiac angiogenesis, restrain fibrous scar formation and thus ameliorate cardiac function in post-MI, via the active regulation of VEGF/VEGFRs signaling pathway