title: OX40 regulates pressure overload-induced cardiac hypertrophy and remodelling via CD4+ T-cells.
abstract: OX40, which belongs to the tumour necrosis factor (TNF)-receptor family, is a costimulatory receptor that can potentiate T-cell receptor signalling on the surface of T-lymphocytes. The role of OX40 in non-immune systems, particularly the cardiovascular system, has not been defined. In the present study, we observed a noticeable increase in OX40 expression during cardiac remodelling in rodent heart. In the present study, cardiac hypertrophy was induced by aortic banding (AB) in OX40 knockout (KO) mice and wild-type (WT) mice. After 8 weeks, the OX40 KO mice showed significantly attenuated cardiac hypertrophy, fibrosis and inflammation as well as preserved cardiac function compared with the WT mice. Follow-up in vitro studies suggested that CD4+T-lymphocyte proliferation and pro-inflammatory cytokine release were significantly decreased, whereas anti-inflammatory cytokine release was considerably increased in OX40 KO mice compared with WT mice as assessed by Cell Counting Kit-8 (CCK-8) assay and ELISA. Co-culturing neonatal rat cardiomyocytes with the activated supernatant of CD4+T-lymphocytes from OX40 KO mice reduced the hypertrophy response. Interestingly, OX40 KO mice with reconstituted CD4+T-lymphocytes presented deteriorated cardiac remodelling. Collectively, our data indicate that OX40 regulates cardiac remodelling via the modulation of CD4+T-lymphocytes.
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
authors: Qing-Qing
authors: QQ
authors: Wu
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
authors: Yuan
authors: Y
authors: Yuan
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
authors: Xiao-Han
authors: XH
authors: Jiang
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
authors: Yang
authors: Y
authors: Xiao
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
authors: Zheng
authors: Z
authors: Yang
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
authors: Zhen-Guo
authors: ZG
authors: Ma
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
authors: Hai-Han
authors: HH
authors: Liao
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
authors: Yuan
authors: Y
authors: Liu
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
authors: Wei
authors: W
authors: Chang
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
authors: Zhou-Yan
authors: ZY
authors: Bian
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China qztang@whu.edu.cn.
authors: Qi-Zhu
authors: QZ
authors: Tang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D053262:Receptors, OX40 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053262:Receptors, OX40
keywords: Ang II; CD4+ T-lymphocytes; OX40; cardiac remodelling; pressure overload