Inhibition of cardiac myocyte maturation by 1,25-dihydroxyvitamin D₃

The signals that regulate cardiac myocyte maturation in the neonatal heart are not completely understood. In our study we examined the effects of 1,25- dihydroxyvitamin D₃ [1,25-(OH)₂D₃] on primary cultures of ventricular myocytes isolated from neonatal rat hearts. Our data show that 1,25-(OH)₂D₃ inhibited an increase in both the muscle-specific form of creatine kinase and V₁ myosin isoenzyme levels in myocytes induced to mature by serum withdrawal. Thus, in contrast to other cell types studied to date, in the heart, 1,25-(OH)₂D₃ blocks cell maturation. Treating cultures with phorbol 12-myristate 13-acetate induced a decrease in the muscle-specific isoenzyme of creatine kinase similar to the effects of 1,25-(OH)₂D₃. Interestingly, we found that staurosporine, a protein kinase-C inhibitor, blunts the effects of 1,25-(OH)₂D₃ and has the opposite effect of phorbol 12-myristate 13- acetate on cultured myocytes induced to mature by serum withdrawal. Thus, our data identify a novel role for 1,25-(OH)₂D₃ in the regulation of myocardial development and suggest that 1,25-(OH)₂D₃ may be acting through a protein kinase-dependent mechanism to maintain cardiac myocytes in an immature state.