血管紧张素II
心脏纤维化
肌成纤维细胞
纤维化
肾素-血管紧张素系统
内科学
内分泌学
转化生长因子
成纤维细胞
血管紧张素受体
心肌纤维化
心室
医学
化学
受体
血压
生物化学
体外
作者
Rui-Rui Chen,Xuehui Fan,Gang Chen,Guangwei Zeng,Yugang Xue,Xiongtao Liu,Chiyao Wang
标识
DOI:10.1016/j.cbi.2019.01.031
摘要
Angiotensin II-related cardiac fibrosis is one of the key pathological changes of the hypertrophied left ventricle in various heart disease. Irisin was recently reported to confer cardio-protective and anti-oxidative effects, while whether it can reverse the renin–angiotensin–aldosterone system(RAAS) activation related(angiotensin II-induced) cardiac fibrosis is unknown. In this study, we found that angiotensin II-induced cardiac dysfunction and fibrotic responses were dampened by irisin treatment in mice. Mechanistically, angiotensin II induced robust ROS generation, which in turn triggered activation of pro-fibrotic TGFβ1-Smad2/3 signaling and subsequent collagen synthesis and fibroblast-myofibroblast transformation in cardiac fibroblasts. In contrast, Irisin treatment suppressed angiotensin II-induced ROS generation, TGFβ1 activation, collagen synthesis and fibroblast-myofibroblast transformation, the effects of which was accompanied by Nrf2 activation and also abolished by a Nrf2 targeted siRNA. Taken together, we here identified irisin as a promising anti-fibrotic therapeutic for angiotensin II-related cardiac fibrosis.
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