論文

査読有り
2016年9月

ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism

NATURE COMMUNICATIONS
  • Zhe Tian
  • ,
  • Keishi Miyata
  • ,
  • Tsuyoshi Kadomatsu
  • ,
  • Haruki Horiguchi
  • ,
  • Hiroyuki Fukushima
  • ,
  • Shugo Tohyama
  • ,
  • Yoshihiro Ujihara
  • ,
  • Takahiro Okumura
  • ,
  • Satoshi Yamaguchi
  • ,
  • Jiabin Zhao
  • ,
  • Motoyoshi Endo
  • ,
  • Jun Morinaga
  • ,
  • Michio Sato
  • ,
  • Taichi Sugizaki
  • ,
  • Shunshun Zhu
  • ,
  • Kazutoyo Terada
  • ,
  • Hisashi Sakaguchi
  • ,
  • Yoshihiro Komohara
  • ,
  • Motohiro Takeya
  • ,
  • Naoki Takeda
  • ,
  • Kimi Araki
  • ,
  • Ichiro Manabe
  • ,
  • Keiichi Fukuda
  • ,
  • Kinya Otsu
  • ,
  • Jun Wada
  • ,
  • Toyoaki Murohara
  • ,
  • Satoshi Mohri
  • ,
  • Jun K. Yamashita
  • ,
  • Motoaki Sano
  • ,
  • Yuichi Oike

7
開始ページ
13016
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/ncomms13016
出版者・発行元
NATURE PUBLISHING GROUP

A cardioprotective response that alters ventricular contractility or promotes cardiomyocyte enlargement occurs with increased workload in conditions such as hypertension. When that response is excessive, pathological cardiac remodelling occurs, which can progress to heart failure, a leading cause of death worldwide. Mechanisms underlying this response are not fully understood. Here, we report that expression of angiopoietin-like protein 2 (ANGPTL2) increases in pathologically-remodeled hearts of mice and humans, while decreased cardiac ANGPTL2 expression occurs in physiological cardiac remodelling induced by endurance training in mice. Mice overexpressing ANGPTL2 in heart show cardiac dysfunction caused by both inactivation of AKT and sarco(endo) plasmic reticulum Ca2+-ATPase (SERCA) 2a signalling and decreased myocardial energy metabolism. Conversely, Angptl2 knockout mice exhibit increased left ventricular contractility and upregulated AKT-SERCA2a signalling and energy metabolism. Finally, ANGPTL2-knockdown in mice subjected to pressure overload ameliorates cardiac dysfunction. Overall, these studies suggest that therapeutic ANGPTL2 suppression could antagonize development of heart failure.

Web of Science ® 被引用回数 : 30

リンク情報
DOI
https://doi.org/10.1038/ncomms13016
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000385457800001&DestApp=WOS_CPL
URL
https://www.ncbi.nlm.nih.gov/pubmed/27677409
URL
http://orcid.org/0000-0003-1468-5170
ID情報
  • DOI : 10.1038/ncomms13016
  • ISSN : 2041-1723
  • ORCIDのPut Code : 43365876
  • Web of Science ID : WOS:000385457800001

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