Viral myocarditis is inflammation of the myocardium mainly caused by a viral infection, and coxsackievirus B3 (CVB3) infection is one of the most common. It is well known that cardiomyocyte apoptosis is involved in the pathogenesis of viral myocarditis. microRNAs (miRNAs, miRs) are endogenous noncoding oligoribonucleotides involved in various pathological conditions, and miR-34a is one of the miRNAs causing apoptosis. Whether miR-34a participates in cardiomyocyte apoptosis during CVB3 infection and the underlying mechanisms is still unclear. In this in vitro study, we found that miR-34a expression increased in cardiomyocytes after CVB3 infection. Furthermore, we found that CVB3 infection augmented histone deacetylase 1 (HDAC1) and Bax expression while inhibiting sirtuin 1 (SIRT1) and Bcl-2 expression, along with the acetylated p53 (Ac-p53) upregulation in cardiomyocytes. The above-mentioned phenomenon was reversed by a miR-34a inhibitor after CVB3 infection. In addition, the Ac-p53 amount increased in CVB3-infected cardiomyocytes, and SRT1720 and trichostatin A (TSA) pretreatment decreased Ac-p53 levels. After pifithrin-alpha pretreatment of CVB3-infected cardiomyocytes, the protein expression level of HDAC1 decreased while that of SIRT1 increased. Moreover, miR-34a expression and CVB3-induced apoptosis of cardiomyocytes were attenuated by pretreatment with SRT1720, TSA, or pifithrin-alpha, accompanied with Bax downregulation and Bcl-2 upregulation. In summary, these data indicate that miR-34a induces cardiomyocyte apoptosis by downregulating SIRT1, and the activation of the SIRT1-p53 pathway contributes to CVB3-induced apoptosis of cardiomyocytes. Thus, miR-34a might serve as a potential therapeutic target because it promotes cardiomyocyte apoptosis through the SIRT1-p53 signaling pathway.
