The Vitamin D Receptor Activator Maxacalcitol Provides Cardioprotective Effects in Diabetes Mellitus.

PURPOSE: Recent reports showed a significant association between vitamin D levels and cardiovascular disease events and mortality. In the current study, we investigated the effect of the vitamin D receptor activator maxacalcitol (OCT) on cardiac damage in a rat model of type 2 diabetes.

METHODS: At 20 weeks of age, the rats were divided into three groups: vehicle-treated (DM), insulin-treated (INS) and OCT-treated (OCT). At 30 weeks, the rats were sacrificed and urinary and blood biochemical analyses and cardiac histological and immunohistochemical analyses were performed. To evaluate the effect of OCT on the renin-angiotensin system, we performed a further study using aliskiren (ALS). At 20 weeks, the diabetic rats were divided into two groups: the ALS-treated group (ALS) and the ALS plus OCT-treated group (ALS + OCT), and we evaluated the renin-angiotensin system (RAS) and cardiac lesions at 30 weeks.

RESULTS: At 30 weeks, despite comparable blood pressure and renal function, heart volume, intracardiac oxidative stress by immunohistological analysis, cardiac and perivascular fibrosis and urinary excretion of 8-hydroxydeoxyguanosine and serum N-terminal pro-brain natriuretic peptide levels were significantly decreased in the OCT group compared to the DM group. mRNA expressions of dihydronicotinamide adenine dinucleotide phosphate (NADPH) p47 subunit and cardiac injury-related markers in the heart were also significantly decreased in the OCT group compared to the DM group. The cardioprotective effect of OCT was preserved even in the context of RAS inhibition.

CONCLUSION: Our results suggest that OCT prevents the development of cardiac damage in DM, independent of RAS inhibition.