Heart Care Info - Heart Disease Prevention & Treatment

HMGB 1 blockade attenuates experimental autoimmune myocarditis possibly by suppressing Th17‐cell expansion

Z Su, C Sun, C Zhou, Y Liu, H Zhu... - European Journal ..., 2011 - Wiley Online Library Abstract High mobility group box 1 (HMGB1), a non-histone nuclear protein, induces inflammatory responses and has been implicated in cardiovascular diseases. Dilated cardiomyopathy (DCM), one of the leading causes of heart failure, is often caused by ...

High mobility group box 1 (HMGB1), a non histone nuclear protein, has been implicated in cardiovascular diseases. Dilated cardiomyopathy (DCM), one of the leading causes of heart failure, is often caused by coxsackievirus B3 triggered myocarditis and promoted by the post infectious autoimmune process. Th17 cells, a novel CD4+ T subset, may be important in the pathogenesis of autoimmune myocarditis. In the present study, we attempted to block HMGB1 function with a monoclonal antibody specific for HMGB1 B box and investigated the effects of the blockade on Th17 cells and experimental autoimmune myocarditis (EAM). After induction of EAM, HMGB1 protein levels were significantly elevated both in the heart and blood. Administration of an anti HMGB1 B box m Ab attenuated cardiac pathological changes and reduced the number of infiltrating inflammatory cells in the heart during EAM. These protective effects of HMGB1 blockade correlated with a reduced number of Th17 cells in local tissues and lower levels of IL 17 in the serum. Furthermore, in vitro, studies demonstrated that HMGB1 promoted Th17 cell expansion. Therefore, we speculate that HMGB1 blockade ameliorates cardiac pathological changes in EAM by suppressing Th17 cells.