Cardioprotective effect of apelin-13 on cardiac performance and remodeling in end-stage heart failure

Abstract

Background: 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 investigators demonstrated that a reduction in myocardial apelin/APJ expression might play a critical role in experimental models of end-stage heart failure (HF). Therefore, we evaluated whether exogenous apelin infusion restores apelin/APJ expression and improves cardiac function in the failing heart of Dahl salt-sensitive hypertensive (DS) rats. Methods and Results: High salt-loaded DS rats were treated with vehicle and pyroglutamylated apelin-13 (Pyr- AP13; 200 μg·kg -1 day -1, IP) from the age of 11 to 18 weeks. Decreased end-systolic elastance and percent fractional shortening in failing rats was significantly ameliorated by Pyr-AP13. Pyr-AP13 effectively inhibited vascular lesion formation and suppressed expression of inflammation factors such as tumor necrosis factor-α and interleukin-1β protein. Downregulation of apelin and APJ expression, and phosphorylation of endothelial nitric oxide synthase at Ser 1177 and Akt at Ser 473 in failing rats was significantly increased by Pyr-AP13. Upregulation of NAD(P)H oxidase p 22phox, p 47phox, and gp 91phox in DS rats was significantly suppressed by Pyr-AP13. Conclusions: Exogenous apelin-13 may ameliorate cardiac dysfunction and remodeling and restore apelin/APJ expression in DS rats with end-stage HF. Thus, apelin-13 may have significant therapeutic potential for end-stage HF.