FIG 7.

Proposed model of the mechanism of HDACI effect on CVB3-induced myocarditis. CVB3 infection induces both proinflammatory cytokine expression and myocardial autophagosome formation. Proinflammatory cytokines secreted by cardiac myocytes trigger the inflammation response, and the myocardial autophagosome supports CVB3 replication, leading to myocardial apoptosis. Both inflammatory response and myocardial apoptosis are thought to be the major contributors to myocarditis. The HDACI-enhanced autophagosome formation results in excessive CVB3 replication, which aggravates apoptotic myocyte damage and consequent myocarditis. To some extent, inflammation response has a cardioprotective effect by limiting CVB3 replication. Thus, HDACI-mediated inhibition of proinflammatory cytokine expression also might enhance CVB3 replication and contribute to the exacerbation of the disease. The arrow indicates positive regulation, and the crossbar indicates negative regulation. The dotted crossbar represents a likely effect. The well-accepted mechanisms of CVB3-induced myocarditis are colored black, and our proposed mechanisms by which HDACI exacerbates this disease are colored red.