Vitamin D: Cardiovascular effects and vascular calcification

The role of vitamin D in skeletal physiology and calcium/phosphate homeostasis is well recognized. This chapter provides an overview of vitamin D in cardiovascular physiology and toxicology. Vitamin D plays a biphasic role in human health, with both insufficiency and intoxication compromising cardiovascular physiology. Vitamin D agonists (VDRAs) are vasculotropic hormones, and vitamin D insufficiency is associated with significant, undesirable changes in cardiovascular physiology and structure. In end-stage renal disease, benefits of pharmacological enhancement of vitamin D receptor (VDR) tone with VDRAs have emerged, likely via improvements in endothelial function and reductions in myocardial hypertrophic responses. Vitamin D intoxication also exerts significant undesirable actions on the cardiovascular system via elevations in serum phosphate and serum calcium/calciproteins, impairment of VSMC elastin biology, and inhibition of protective vascular PTH/PTHrP receptor signaling. Histoanatomic, molecular, and ethnic heterogeneities are emerging in the pathobiology of arteriosclerotic disease; these heterogeneities confound straightforward extrapolation of the downsides of insufficiency to benefits with repletion or supplementation. Dynamic interactions between the parathyroids, kidneys, and bone determine the toxicity threshold for vitamin D and calcium-i.e. whether hypervitaminosis D or excessive calcium intake is also associated with toxicity. The relationships between the VDR, its non-nuclear role in mitochondrial function and cardiovascular oxidative stress signaling have yet to be detailed.