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

AbstractBACKGROUND:
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.
AuthorsWataru Koguchi, Naohiko Kobayashi, Hiroshi Takeshima, Mayuko Ishikawa, Fumihiro Sugiyama, Toshihiko Ishimitsu
JournalCirculation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 76 Issue 1 Pg. 137-44 ( 2012) ISSN: 1347-4820 [Electronic] Japan
PMID22082814 (Publication Type: Journal Article)
Chemical References
  • Apelin Receptors
  • Aplnr protein, rat
  • Cardiotonic Agents
  • Intercellular Signaling Peptides and Proteins
  • Receptors, G-Protein-Coupled
  • apelin-13 peptide
  • Nitric Oxide Synthase Type III
Topics
  • Animals
  • Apelin Receptors
  • Blood Pressure (drug effects, physiology)
  • Cardiotonic Agents (pharmacology, therapeutic use)
  • Disease Models, Animal
  • Heart (drug effects, physiopathology)
  • Heart Failure (drug therapy, physiopathology)
  • Intercellular Signaling Peptides and Proteins (pharmacology, physiology, therapeutic use)
  • Male
  • Nitric Oxide Synthase Type III (metabolism)
  • Phosphorylation
  • Rats
  • Rats, Inbred Dahl
  • Receptors, G-Protein-Coupled (physiology)
  • Signal Transduction (drug effects, physiology)
  • Systole (drug effects, physiology)
  • Ventricular Remodeling (drug effects, physiology)

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