Cardioprotective Effect of Apelin-13 on Cardiac Performance and Remodeling in End-Stage Heart Failure

• Koguchi Wataru

  Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University School of Medicine

• Kobayashi Naohiko

  Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University School of Medicine

• Takeshima Hiroshi

  Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University School of Medicine

• Ishikawa Mayuko

  Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University School of Medicine

• Sugiyama Fumihiro

  Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University School of Medicine

• Ishimitsu Toshihiko

  Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University School of Medicine

抄録

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 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. (Circ J 2012; 76: 137-144)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 76 (1), 137-144, 2012

  一般社団法人 日本循環器学会

キーワード

• Apelin
• Cardiac function
• Heart failure
• Remodeling

詳細情報

• CRID: 1390001205102617344
• NII論文ID: 10030034426
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-11-0689
• ISSN: 13474820
• ISSN: 13469843
• Web Site: http://www.jstage.jst.go.jp/article/circj/76/1/76_CJ-11-0689/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2014342763
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可