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タイトル: | ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism |
著者: | Tian, Zhe Miyata, Keishi Kadomatsu, Tsuyoshi Horiguchi, Haruki Fukushima, Hiroyuki Tohyama, Shugo Ujihara, Yoshihiro Okumura, Takahiro Yamaguchi, Satoshi Zhao, Jiabin Endo, Motoyoshi Morinaga, Jun Sato, Michio Sugizaki, Taichi Zhu, Shunshun Terada, Kazutoyo Sakaguchi, Hisashi Komohara, Yoshihiro Takeya, Motohiro Takeda, Naoki Araki, Kimi Manabe, Ichiro Fukuda, Keiichi Otsu, Kinya Wada, Jun Murohara, Toyoaki Mohri, Satoshi Yamashita, Jun K. Sano, Motoaki Oike, Yuichi |
著者名の別形: | 福島, 弘之 山下, 潤 |
キーワード: | Heart failure |
発行日: | 28-Sep-2016 |
出版者: | Springer Nature |
誌名: | Nature Communications |
巻: | 7 |
論文番号: | 13016 |
抄録: | 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 Ca(2+)-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. |
著作権等: | © The Author(s) 2016 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. |
URI: | http://hdl.handle.net/2433/227065 |
DOI(出版社版): | 10.1038/ncomms13016 |
PubMed ID: | 27677409 |
出現コレクション: | 学術雑誌掲載論文等 |
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