Vinexin-β is one of the adaptor proteins that are primarily involved in signal transduction and cytoskeletal organization under various pathological conditions, including cardiac hypertrophy. However, the role of Vinexin-β in myocardial infarction (MI) remains unknown. In this study, dramatically up-regulated Vinexin-β expression was observed in both ischaemic human hearts and infarcted animal hearts. To explore the potential involvement of Vinexin-β in MI further, we induced MI injury in global Vinexin-β-knockout mice and wild-type (WT) controls as well as in mice with cardiac-specific over-expression of the human Vinexin-β gene-transgenic (TG) and -non-transgenic (NTG) littermates. Compared with that observed in WT controls, Vinexin-β deficiency significantly decreased MI-induced infarct size, concomitant with an improved cardiac function, leading to an increase in the survival rate. The myocardial apoptosis in the border zone was dramatically reduced by Vinexin-β deficiency, resulting from the altered expression of apoptotic factors. Furthermore, Vinexin-β depletion mitigated the inflammatory response, as evidenced by reduced inflammatory cell infiltration, decreased expression of cytokines and the inactivation of NF-κB (nuclear factor κB) signalling. In contrast, Vinexin-β-TG mice were much more susceptible to MI injury compared with NTG controls. Further mechanism analyses suggested that Vinexin-β exerted detrimental effects largely dependent on blocking AKT signalling. The effects and mechanisms of Vinexin-β on MI observed in vivo were further confirmed by our in vitro assays. When collected, these data demonstrate for the first time that Vinexin-β increases MI-induced mortality and worsens cardiac dysfunction through aggravation of myocardial apoptosis and inflammatory response.
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March 27 2015
Vinexin-β exacerbates cardiac dysfunction post-myocardial infarction via mediating apoptotic and inflammatory responses Available to Purchase
Xiaoxiong Liu;
Xiaoxiong Liu
*Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
†Cardiovascular Research Institute, Wuhan University, Wuhan, China
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Nian Wan;
Nian Wan
*Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
†Cardiovascular Research Institute, Wuhan University, Wuhan, China
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Xiao-Jing Zhang;
Xiao-Jing Zhang
‡State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
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Yichao Zhao;
Yichao Zhao
§Department of Cardiology, Shanghai Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
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Yan Zhang;
Yan Zhang
*Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
†Cardiovascular Research Institute, Wuhan University, Wuhan, China
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Gangying Hu;
Gangying Hu
*Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
†Cardiovascular Research Institute, Wuhan University, Wuhan, China
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Fengwei Wan;
Fengwei Wan
∥Department of Emergency, Second Artillery General Hospital of Chinese People's Liberation Army Qinghe Clinic, Beijing, China
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Rui Zhang;
Rui Zhang
†Cardiovascular Research Institute, Wuhan University, Wuhan, China
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Xueyong Zhu;
Xueyong Zhu
†Cardiovascular Research Institute, Wuhan University, Wuhan, China
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Hao Xia;
*Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
†Cardiovascular Research Institute, Wuhan University, Wuhan, China
Correspondence: Dr Hao Xia (email [email protected]) or Dr Hongliang Li ([email protected]).
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Hongliang Li
*Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
†Cardiovascular Research Institute, Wuhan University, Wuhan, China
Correspondence: Dr Hao Xia (email [email protected]) or Dr Hongliang Li ([email protected]).
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Publisher: Portland Press Ltd
Received:
October 13 2014
Revision Received:
January 26 2015
Accepted:
February 06 2015
Accepted Manuscript online:
February 06 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 128 (12): 923–936.
Article history
Received:
October 13 2014
Revision Received:
January 26 2015
Accepted:
February 06 2015
Accepted Manuscript online:
February 06 2015
Citation
Xiaoxiong Liu, Nian Wan, Xiao-Jing Zhang, Yichao Zhao, Yan Zhang, Gangying Hu, Fengwei Wan, Rui Zhang, Xueyong Zhu, Hao Xia, Hongliang Li; Vinexin-β exacerbates cardiac dysfunction post-myocardial infarction via mediating apoptotic and inflammatory responses. Clin Sci (Lond) 1 June 2015; 128 (12): 923–936. doi: https://doi.org/10.1042/CS20140648
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