Cardiomyocyte‐derived HMGB1 takes a protective role in CVB3‐induced viral myocarditis via inhibiting cardiac apoptosis

Abstract

AbstractCoxsackievirus B3 (CVB3)‐induced viral myocarditis (VMC) is characterized by immune cell infiltration and myocardial damage. High mobility group box 1 (HMGB1) is a highly conserved nuclear DNA‐binding protein that participates in DNA replication, transcriptional regulation, repair response and inflammatory response in different disease models. To investigate the exact function of HMGB1 in CVB3‐induced VMC, we crossed Hmgb1‐floxed (Hmgb1f/f) mice with mice carrying a suitable Cre recombinase transgenic strain to achieve conditional inactivation of the Hmgb1 gene in a cardiomyocyte‐specific manner and to establish myocarditis. In this study, we found that cardiomyocyte‐specific Hmgb1‐deficient (Hmgb1f/fTgCre/+) mice exhibited exacerbated myocardial injury. Hmgb1‐deficient cardiomyocytes may promote early apoptosis via the p53‐mediated Bax mitochondrial pathway, as evidenced by the higher localization of p53 protein in the cytosol of Hmgb1‐deficient cardiomyocytes upon CVB3 infection. Moreover, cardiomyocyte Hmgb1‐deficient mice are more susceptible to cardiac dysfunction after infection. This study provides new insights into HMGB1 in VMC pathogenesis and a strategy for appropriate blocking of HMGB1 in the clinical treatment of VMC.