NAD

BACKGROUND: Diabetes is a risk factor of heart failure and promotes cardiac dysfunction. Diabetic tissues are associated with NAD(+) redox imbalance; however, the hypothesis that NAD(+) redox imbalance causes diabetic cardiomyopathy (DCM) has not been tested. This investigation employed mouse models with altered NAD(+) redox balance to test this hypothesis. METHODS: Diabetic stress was induced in mice by streptozotocin. Cardiac function was measured by echocardiography. Heart and plasma samples were collected for biochemical, histological and molecular analyses. Two mouse models with altered NAD(+) redox states (cardiac-specific knockout mice of Ndufs4, cKO; nicotinamide phosphoribosyltransferase transgenic mice, NAMPT) were used. RESULTS: Diabetic stress caused cardiac dysfunction and lowered NAD(+)/NADH in wild-type mice. Mice with lowered cardiac NAD(+)/NADH without baseline dysfunction, cKO mice, were challenged with chronic diabetic stress. NAD(+) redox imbalance in cKO hearts exacerbated systolic (FS: 27.6% vs 36.9% at 4-week, male cohort, P