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
|
巻 | 7
|
号 | 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
|