Vinexin-{beta} Exacerbates Cardiac Dysfunction Post-Myocardial Infarction via Mediating Apoptotic and Inflammatory Responses

In this study, dramatically upregulated Vinexin-β expressions were observed in both the ischemic human hearts and infarcted animal hearts. To further explore the potential involvement of Vinexin-β in MI, we induced MI injury in global Vinexin-β knockout (KO) mice and wild-type (WT) controls as well as mice with cardiac-specific overexpression of the human Vinexin-β gene (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 improvement in 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 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.Correctively, these data demonstrate for the first time that Vinexin-β increases MI-induced morta...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research