Selective Knockout of the Vitamin D Receptor in the Heart Results in Cardiac Hypertrophy

The report by Dr Chen and colleagues, published in this issue of Circulation , “Cardiomyocyte-Specific Deletion of the Vitamin D Receptor Gene Results In Cardiac Hypertrophy,” is important and timely.1 This study extends and supports other studies that have demonstrated that vitamin D and the vitamin D receptor (VDR) signaling system possess antihypertrophic activity in the heart. The study also furthers our knowledge of this action by demonstrating an involvement of the prohypertrophic calcineurin/nuclear factor of activated T-cells/modulatory calcineurin-interacting protein-1 pathway. Thereby, they identify a potential mechanism to account for the reported beneficial effects of vitamin D on the cardiovascular system. To respond to the question posed in the title of this editorial, “Is the heart a drugable target for vitamin D receptor agonists?” Chen et al's report makes an affirmative response more plausible.Article see p 1838The first studies to demonstrate a connection between cardiovascular homeostasis and vitamin D status used the established rat model of vitamin D deficiency.2–4 The notion of an involvement of the vitamin D endocrine system with cardiovascular function began >25 years ago by our identification of the VDR in rat cardiac myocytes, and this led us to the physiological studies to establish relevance.5 These animal studies established a connection between vitamin D deficiency and cardiovascular dysfunctions, including cardiac hypertrophy, fibrosis, hypertension, and the elevation of serum calcium, parathyroid hormone, and renin levels. These reports supported a role for vitamin D in maintaining cardiovascular homeostasis through both the direct action of 1,25-dihydroxyvitamin D on cardiomyocyte VDR and indirect actions on circulating hormones and calcium. Our studies in rats maintained on a vitamin D-deficient diet revealed that ventricular muscle mass and contractile function were both markedly enhanced. Increased systolic blood pressure, renin levels, hydroxyproline, and serum creatine phosphokinase were reported, …