Pioglitazone Alleviates Cardiac Fibrosis and Inhibits Endothelial to Mesenchymal Transition Induced by Pressure Overload

被引:28
作者
Wei, Wen-Ying
Zhang, Ning
Li, Ling-Li
Ma, Zhen-Guo
Xu, Man
Yuan, Yu-Pei
Deng, Wei
Tang, Qi-Zhu [1 ,2 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Cardiol, Jiefang Rd 238, Wuhan 430060, Hubei, Peoples R China
[2] Wuhan Univ, Cardiovasc Res Inst, Jiefang Rd 238, Wuhan 430060, Hubei, Peoples R China
关键词
Ppar-gamma; Pioglitazone; Cardiac fibrosis; EndMT; ACTIVATED RECEPTOR-GAMMA; FIBROBLASTS;
D O I
10.1159/000486220
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background/Aims: Cardiac fibrosis, characterized by an unbalanced production and degradation of extracellular matrix components, is a common pathophysiology of multiple cardiovascular diseases. Recent studies suggested that endothelial to mesenchymal transition (EndMT) could be a source of activated fibroblasts and contribute to cardiac fibrosis. Here, the role of pioglitazone (PIO) in cardiac fibrosis and EndMT was elaborated. Methods: Male C57BL/6 mice were subjected to aortic banding (AB), which was used to construct a model of pressure overload-induced cardiac hypertrophy. PIO and GW9662 was given for 4 weeks to detect the effects of PIO on EndMT. Results: Our results showed PIO treatment attenuated cardiac hypertrophy, dysfunction and fibrosis response to pressure overload. Mechanistically, PIO suppressed the TGF-beta/Smad signaling pathway activated by 4-week AB surgery. Moreover, PIO dramatically inhibited EndMT in vivo and in vitro stimulated by pressure overload or TGF-beta. A selective antagonist of PPAR-gamma, GW9662, neutralized the anti-fibrotic effect and abolished the inhibitory effect of EndMT during the treatment of PIO. Conclusion: Our data implied that PIO exerts an alleviative effect on cardiac fibrosis via inhibition of the TGF-beta/Smad signaling pathway and EndMT by activating PPAR-gamma. (C) 2018 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:26 / 36
页数:11
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