Cardiomyocyte specific CD38 deletion protects heart from acute myocardial infarction by activating Sirt3 signaling pathway.

Acute myocardial infarction (AMI) is serious disease with high morbidity and mortality worldwide. CD38 is an important metabolic enzyme and plays an important role in a variety of diseases. Our previous studies demonstrated that CD38 deficiency significantly reduced Ang-II-induced ventricular hypertrophy and cardiac ischemia-reperfusion injury. However, the roles of cardiomyocytic CD38 in acute myocardial infarction (AMI) remain unknown. Here, we reported that cardiomyocyte-specific CD38 deficiency (CD38(CKO)) significantly improved heart functions in AMI. We observed that CD38(CKO) remarkably reduced the fibrosis at the peri-infarct area, and inhibited the apoptosis of cardiomyocytes in infarcted area by elevating the ratio of mitochondrial Bcl2/Bax expression and increased the expressions of the mitochondrial fusion proteins Mfn1 and Mfn2 in the early stage of AMI. Consistently, knockdown of CD38 protected hypoxia-induced apoptosis in cardiomyocytes by increasing the ratio of Bcl2/Bax expression and decreasing cleaved caspase-3. More importantly, 3-TYP, a Sirt3 inhibitor, significantly increased hypoxia-induced apoptosis in CD38-deficient primary cardiomyocytes. In conclusion, our results demonstrated that CD38(CKO) suppressed apoptosis of cardiomyocytes in the infracted area of heart via activating NAD(+)/Sirt3-mediated signaling pathways.