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Title: ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism
Authors: 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
Author's alias: 福島, 弘之
山下, 潤
Keywords: Heart failure
Issue Date: 28-Sep-2016
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 7
Thesis number: 13016
Abstract: 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.
Rights: © 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(Published Version): 10.1038/ncomms13016
Appears in Collections:Journal Articles

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