Protective and toxic effects of vitamin D on vascular calcification: clinical implications.
The presence of vascular calcification (VC) is a predictor of poor survival in the general population. The development of VC is an active process that requires a pre-existing injury as an inducer and promoting factors such as hyperphosphatemia and hypercalcemia, as well as a deficiency in calcification repressor factors. Vascular smooth muscle cells possess an endogenous enzyme system for the biosynthesis of the vitamin D hormone calcitriol from its precursor 25-hydroxyvitamin D and also a cytosolic calcitriol receptor, indicating that the vasculature is an important target tissue for vitamin D. The toxic effects of supra-physiological vitamin D dosages on the vasculature have been known for several decades. Recent experimental data also demonstrate important physiological effects of vitamin D on factors that are protective for vascular health. This review article summarises the molecular basis of protective and toxic vitamin D actions on the vasculature. Chronic kidney disease can be considered as a human model of severe VC and poor survival. The disease is associated with calcitriol deficiency, hyperparathyroidism, and hyperphosphatemia. Evidence is increasing that phosphate overload plays a key role in the process of VC in chronic kidney disease. The first clinical studies indicate that vitamin D receptor activation can improve survival in these patients. Although less severe than in chronic kidney disease, vitamin D deficiency and secondary hyperparathyroidism are also frequent in the general population, especially in elderly and obese subjects. Future studies should focus on the impact of vitamin D deficiency on VC and clinical outcome in these groups.
Department of Thoracic- and Cardiovascular Surgery, Heart and Diabetes Center North-Rhine Westfalia, University Hospital of Ruhr University Bochum, Georgstrasse 11, 32545 Bad Oeynhausen, Germany. azittermann@hdz-nrw.de
Armin
A
Zittermann
Reiner
R
Koerfer
D000818:Animals; D002114:Calcinosis / Q000139:chemically induced* / Q000517:prevention & control*; D002908:Chronic Disease; D004703:Endocrine System / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000503:physiopathology; D008954:Models, Biological; D014807:Vitamin D / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D014807:Vitamin D