aFGF Targeted Mediated by Novel Nanoparticles-Microbubble Complex Combined With Ultrasound-Targeted Microbubble Destruction attenuates Doxorubicin-Induced Heart Failure via Anti-Apoptosis and Promoting Cardiac Angiogenesis

Abstract

The purpose of this study was to evaluate the protective effect of acidic fibroblast growth factor targeted mediated by novel nanoparticles–cationic lipid microbubbles complex (aFGF–NP + CPMBs) combined with ultrasound targeted microbubble destruction (UTMD)on doxorubicin–induced heart failure (HF)and its mechanism. Heart failure rats induced by intraperitoneal injection with doxorubicin (DOX) to achieve cummulative dose of 15mg/kg for continuous 6 weeks showed left ventricular dysfunction, seriously oxidative stress, cardiomyocyte apoptosis, and decrease of myocardial vascular density. In contrast, aFGF–NP + CPMBs combined with UTMD therapy (3ug/kg, caudal vein injection, twice a week, 6weeks)prominently ameliorated left ventricular dysfunction by increased ejection fraction (EF) and fractional shortening (FS), decreased brain natriuretic peptide (BNP); strengthened the ability of antioxidant stress confirmed by increasing the activity of SOD and reducing the production of MDA; exerted the effect of anti–cardiomyocyte apoptosis and promotion angiogenesis by inhibited Bax expression and increased Bcl–2 expression and platelet endothelial cell adhesion molecule (CD31) expression. Taken together, the research suggested that aFGF targeted mediated by novel nanoparticles–cationic lipid microbubbles complex combined with UTMD should be a promising targeted treatment for heart failure.