title: Vinexin-β exacerbates cardiac dysfunction post-myocardial infarction via mediating apoptotic and inflammatory responses.
abstract: 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.
authors: *Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Xiaoxiong
authors: X
authors: Liu
authors: *Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Nian
authors: N
authors: Wan
authors: ‡State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors: Xiao-Jing
authors: XJ
authors: Zhang
authors: §Department of Cardiology, Shanghai Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors: Yichao
authors: Y
authors: Zhao
authors: *Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Yan
authors: Y
authors: Zhang
authors: *Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Gangying
authors: G
authors: Hu
authors: ∥Department of Emergency, Second Artillery General Hospital of Chinese People's Liberation Army Qinghe Clinic, Beijing, China.
authors: Fengwei
authors: F
authors: Wan
authors: †Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors: Rui
authors: R
authors: Zhang
authors: †Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors: Xueyong
authors: X
authors: Zhu
authors: *Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Hao
authors: H
authors: Xia
authors: *Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Hongliang
authors: H
authors: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018345:Mice, Knockout; D008875:Middle Aged; D009124:Muscle Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D017202:Myocardial Ischemia / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009124:Muscle Proteins; C486523:SORBS3 protein, human; C117452:Sorbs3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt