Calumenin relieves cardiac injury by inhibiting ERS-initiated apoptosis during viral myocarditis

Viral myocarditis (VMC) is a common disease causing heart failure (HF) for which no specific treatments are available. As Apoptosis of cardiomyoctes is a hallmark of VMC and HF, strategies targeting Apoptosis are an effective way of prevention and treatment of HF. Recent studies found endoplasmic reticulum stress (ERS) reaction is a new signal transduction pathway mediating Apoptosis. Calumenin protein (CP) is located within the endoplasmic reticulum CA²⁺ binding proteins, and is important in ER-initiated Apoptosis. The aim of this study was to investigate whether the function of CP was influenced in cardiomyocytes infected by coxsackievirus B3. The expression of CP was down-regulated in cardiomyocytes infected by coxsackievirus B3. TUNEL studies showed that Apoptosis was increased in CP-deficient and ΔCP-mutant cardiomyocytes infected by coxsackievirus B3. Additionally, ERS-associated proteins (GRP78, p-PERK, p-eIF2α, ATF4 and CHOP) were up-regulated in coxsackievirus B3-infected CP-deficient and ΔCP-mutant cardiomyocytes compared to wild type control cells. These results suggested ER-initiated Apoptosis was induced by coxsackievirus B3-infected cardiomyocytes and caused Apoptosis through ER stress. CP can relieve ERS-initiated Apoptosis in viral myocarditis.