Impact of vitamin D system on ventricular remodeling

The micronutrient vitamin D has long been appreciated for its role in the homeostasis of bone and in the prevention of rickets. Many studies have shown that vitamin D supplementation may also be effective in the prevention and treatment of disorders of the immune system and inflammation, as well as of diseases such as diabetes, cancer and osteoarthritis. There is growing evidence sustaining an important role for vitamin D on heart health as well. Recent studies have demonstrated that vitamin D deficiency is very common in patients affected by chronic renal disease or heart failure, and it is associated with poor outcome among these patients. Heart failure has its origins rooted in adverse structural, biochemical and molecular remodeling of myocardium. Vitamin D receptors (VDR) are widespread in the myocardial cellular constituents, including cardiomyocytes, thus justifying an in-depth analysis of how vitamin D accounts for the causes and consequences of adverse heart remodeling. Vitamin D effects are translated at the cellular level through the activation of the specific nuclear receptor by the active metabolite of vitamin D, 1,25-dihydroxyvitamin D. Vitamin D is a negative regulator of the renin-angiotensin system and acts to reduce hypertrophic, apoptotic and pro-fibrotic gene expression. Mechanistic insights were gained mainly by experimental studies on VDR-deficient mice, which develop hypertension and adverse cardiac remodeling mediated via the renin-angiotensin system. In addition, studies on mouse models of cardiomyocyte-specific deletion of VDR demonstrated an increase in myocyte size and left ventricular hypertrophy in the conditional knockout. Given the clinical impact of adverse ventricular remodeling, this review summarizes current knowledge on vitamin D and its biology in heart failure to extend our understanding of factors that may act against ventricular hypertrophy and abnormal geometry.