title: Toll-like receptor 5 deficiency attenuates interstitial cardiac fibrosis and dysfunction induced by pressure overload by inhibiting inflammation and the endothelial-mesenchymal transition.
abstract: Vascular dysfunction, characterized by the endothelial-to-mesenchymal transition (EndMT), contributes to the development of cardiac fibrosis induced by pressure overload. Toll-like receptor (TLR)5 is a member of the TLR family that is expressed on not only immune cells but also nonimmune cells including cardiomyocytes and vascular endothelial cells. The level of TLR5 expression on endothelial cells is low under normal circumstances but is increased in response to stimuli such as pressure overload. The aim of this study was to investigate the importance of TLR5 in cardiac endothelial dysfunction during the development of cardiac fibrosis induced by pressure overload. Global TLR5-deficient mice and wild-type littermates underwent aortic banding (AB) for 8weeks to induce cardiac fibrosis, hypertrophy and dysfunction. The deficiency of TLR5 in this model exerted no basal effects but attenuated the cardiac fibrosis, hypertrophy and dysfunction induced by pressure overload. AB-induced endothelial TLR5 activation enhanced the development of cardiac fibrosis independent of cardiomyocyte hypertrophy and triggered left ventricular dysfunction. TLR5-deficient mice also exhibited ameliorated myocardial pro-inflammatory cytokine expression and macrophage infiltration and inhibited the EndMT, all of which contribute to the development of cardiac fibrosis. These findings suggest that TLR5 triggers inflammatory responses and promotes the EndMT, which may be an important mechanism underlying the promotion of cardiac fibrosis and left ventricular dysfunction during pressure overload.
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China.
authors: Yuan
authors: Y
authors: Liu
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China.
authors: Zhe-Fu
authors: ZF
authors: Hu
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China.
authors: Hai-Han
authors: HH
authors: Liao
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China.
authors: Wei
authors: W
authors: Liu
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China.
authors: Juan
authors: J
authors: Liu
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China.
authors: Zhen-Guo
authors: ZG
authors: Ma
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China.
authors: Qing-Qing
authors: QQ
authors: Wu
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China.
authors: Man
authors: M
authors: Xu
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China.
authors: Ning
authors: N
authors: Zhang
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China.
authors: Yao
authors: Y
authors: Zhang
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China.
authors: Zhou-Yan
authors: ZY
authors: Bian
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei 430060, PR China; Cardiovascular Research Institute of Wuhan University, Hubei, PR China. Electronic address: qztang@whu.edu.cn.
authors: Qi-Zhu
authors: QZ
authors: Tang
keywords: Cardiac fibrosis; Endothelial-to-mesenchymal transition; Endothelium; Toll-like receptor 5