title: 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.
  
  
  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.
authors.affiliation: Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University School of Medicine, Tochigi, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Koguchi
authors.forename: Naohiko
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
authors.forename: Mayuko
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sugiyama
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ishimitsu
mesh_terms: D000818:Animals; D000075244:Apelin Receptors; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D020303:Rats, Inbred Dahl; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013599:Systole / Q000187:drug effects / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
chemical_list: D000075244:Apelin Receptors; C491284:Aplnr protein, rat; D002316:Cardiotonic Agents; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C495199:apelin-13 peptide; D052250:Nitric Oxide Synthase Type III