Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Heart Failure
Cardioprotective Effect of Apelin-13 on Cardiac Performance and Remodeling in End-Stage Heart Failure
Wataru KoguchiNaohiko KobayashiHiroshi TakeshimaMayuko IshikawaFumihiro SugiyamaToshihiko Ishimitsu
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2012 Volume 76 Issue 1 Pages 137-144


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; 200μg·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 Ser1177 and Akt at Ser473 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. 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. (Circ J 2012; 76: 137-144)

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