Cardioprotective Effect of Apelin-13 on Cardiac Performance and Remodeling in Dahl rats with End-Stage Heart Failure

Apelin and its cognate G protein-coupled receptor APJ constitute a signaling pathway with a positive inotropic effect on cardiac function. Recently, we and other investigator demonstrated that reduction in myocardial apelin/APJ expression might play a critical role in experimental models with end-stage heart failure. Therefore, we evaluate whether exogenous apelin infusion restores apelin/APJ expression and improves cardiac function in failing heart of Dahl salt-sensitive hypertensive (DS) rats. High salt-loaded DS rats were treated with vehicle and pyroglutamylated apelin-13 (Pyr-AP13; 200μg/kg per day, ip) from the age of 11 to 18 weeks. Decreased end-systolic elastance (Ees) and percent fractional shortening in failing rats was significantly ameliorated by Pyr-AP13. Pyr-AP13 effectively inhibited the vascular lesion formation and suppressed fibrosis factors such as procollagen type I and III and fibronectin protein expression. Downregulation of apelin and APJ expression, and phosphorylation of Akt and eNOS in failing rats was significantly increased by Pyr-AP13. Upregulation of NAD(P)H oxidase p22phox, p47phox, and gp91phox in DS rats was significantly suppressed by Pyr-AP13. These findings suggest that exogenous apelin-13 infusion may ameliorate cardiac dysfunction and remodeling and restore apelin/APJ expression in DS rats with end-stage heart failure. Thus, apelin infusion may have significant therapeutic potential in the treatment of end-stage heart failure.