ID 113034
タイトル別表記
INSL6 Protective Effects in Heart Failure
著者
Maruyama, Sonomi Boston University School of Medicine
Wu, Chia-Ling Boston University School of Medicine
Zhang, Dongying Boston University School of Medicine
Li, Pei-Hsuan Boston University School of Medicine
Wu, Fangzhou Indiana University
Duffen, Jennifer Parker Boston University School of Medicine
Yao, Rouan Boston University School of Medicine
Jardin, Blake Boston University School of Medicine
Adham, Ibrahim M. University Medical Center Göttingen
Law, Ronald Takeda Pharmaceuticals International Co
Berger, Joel Takeda Pharmaceuticals International Co
Marchi, Richard Di Indiana University
Walsh, Kenneth Boston University School of Medicine|University of Virginia School of Medicine
キーワード
anti–cardiac remodeling
anti-fibrosis
heart failure
relaxin family protein
資料タイプ
学術雑誌論文
抄録
Background
The insulin/insulin‐like growth factor/relaxin family represents a group of structurally related but functionally diverse proteins. The family member relaxin‐2 has been evaluated in clinical trials for its efficacy in the treatment of acute heart failure. In this study, we assessed the role of insulin‐like peptide 6 (INSL6), another member of this protein family, in murine heart failure models using genetic loss‐of‐function and protein delivery methods.
Methods and Results
Insl6‐deficient and wild‐type (C57BL/6N) mice were administered angiotensin II or isoproterenol via continuous infusion with an osmotic pump or via intraperitoneal injection once a day, respectively, for 2 weeks. In both models, Insl6‐knockout mice exhibited greater cardiac systolic dysfunction and left ventricular dilatation. Cardiac dysfunction in the Insl6‐knockout mice was associated with more extensive cardiac fibrosis and greater expression of fibrosis‐associated genes. The continuous infusion of chemically synthesized INSL6 significantly attenuated left ventricular systolic dysfunction and cardiac fibrosis induced by isoproterenol infusion. Gene expression profiling suggests liver X receptor/retinoid X receptor signaling is activated in the isoproterenol‐challenged hearts treated with INSL6 protein.
Conclusions
Endogenous Insl6 protein inhibits cardiac systolic dysfunction and cardiac fibrosis in angiotensin II– and isoproterenol‐induced cardiac stress models. The administration of recombinant INSL6 protein could have utility for the treatment of heart failure and cardiac fibrosis.
掲載誌名
Journal of the American Heart Association
ISSN
20479980
出版者
The American Heart Association|Wiley
7
12
開始ページ
e008441
発行日
2018-06-13
権利情報
Copyright © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系