Trehalose induces B cell autophagy to alleviate myocardial injury via the AMPK/ULK1 signalling pathway in acute viral myocarditis induced by Coxsackie virus B3

Viral myocarditis (VMC) is the main cause of sudden acute heart failure and cardiac death in adolescents; however, treatment for VMC is limited. Trehalose is a natural non-reductive disaccharide that protects against cardiovascular diseases by inducing autophagy. The protective effect of trehalose on VMC and the specific mechanism remains unclear. In this study, we established a VMC mouse model, treated with trehalose in vivo, and cultured B cells from VMC mice with trehalose in vitro to elucidate the effect of trehalose on B cells in acute VMC. Trehalose alleviated myocardial injury in VMC mice and increased the number of autophagosomes, LC3II/LC3I ratio, and expression level of LAMP2, whereas it decreased the expression of p62 in VMC-B cells. Bafilomycin A1 suppressed VMC-B cell autophagy induced by trehalose. At the mechanistic level, trehalose treatment significantly upregulated the phosphorylation of AMPK and ULK1 in VMC-B cells. Dorsomorphin and SBI-0206965 abolished the increased phosphorylation level and altered the expression levels of autophagy-related proteins. In conclusion, trehalose alleviates myocardial inflammatory damage of VMC by inducing B cell autophagy, mediated by the AMPK/ULK1 signalling pathway. Thus, trehalose may be a potentially useful molecule for alleviating myocardial injury in VMC.