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

Circ J. 2012;76(1):137-44. doi: 10.1253/circj.cj-11-0689. Epub 2011 Nov 12.


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 Ser(1177) and Akt at Ser(473) in failing rats was significantly increased by Pyr-AP13. Upregulation of NAD(P)H oxidase p22(phox), p47(phox), and gp91(phox) 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.

MeSH terms

  • Animals
  • Apelin Receptors
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use
  • Disease Models, Animal
  • Heart / drug effects
  • Heart / physiopathology*
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology*
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Intercellular Signaling Peptides and Proteins / physiology
  • Intercellular Signaling Peptides and Proteins / therapeutic use*
  • Male
  • Nitric Oxide Synthase Type III / metabolism
  • Phosphorylation
  • Rats
  • Rats, Inbred Dahl
  • Receptors, G-Protein-Coupled / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Systole / drug effects
  • Systole / physiology
  • Ventricular Remodeling / drug effects
  • Ventricular Remodeling / physiology*


  • Apelin Receptors
  • Aplnr protein, rat
  • Cardiotonic Agents
  • Intercellular Signaling Peptides and Proteins
  • Receptors, G-Protein-Coupled
  • apelin-13 peptide
  • Nitric Oxide Synthase Type III