1. Role of local versus systemic vitamin D receptors in vascular calcification.
- Author
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Lomashvili KA, Wang X, and O'Neill WC
- Subjects
- Adenine, Animals, Aorta drug effects, Aorta metabolism, Aorta transplantation, Disease Models, Animal, Female, Genetic Markers, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Smooth, Vascular metabolism, Muscle, Smooth, Vascular pathology, Muscle, Smooth, Vascular transplantation, RNA, Messenger metabolism, Rats, Receptors, Calcitriol deficiency, Receptors, Calcitriol genetics, Receptors, Calcitriol metabolism, Steroid Hydroxylases genetics, Steroid Hydroxylases metabolism, Tissue Culture Techniques, Up-Regulation, Uremia chemically induced, Uremia genetics, Uremia metabolism, Vascular Calcification genetics, Vascular Calcification metabolism, Vascular Calcification pathology, Vitamin D3 24-Hydroxylase, Calcitriol toxicity, Muscle, Smooth, Vascular drug effects, Receptors, Calcitriol agonists, Uremia drug therapy, Vascular Calcification chemically induced
- Abstract
Objective: Calcitriol and various analogs are commonly used to suppress secondary hyperparathyroidism in chronic kidney disease but may also exacerbate vascular calcification. Although this could be because of increased intestinal calcium and phosphate absorption, direct effects through vitamin D receptors (VDRs) on vascular smooth muscle have also been proposed., Approach and Results: The role of these receptors was investigated by examining gene regulation in rat aortas treated with calcitriol ex vivo and in vivo and by transplanting aortas from VDR-null (VDR(-/-)) mice into wild-type mice before induction of uremia and treatment with calcitriol. In cultured rat aortas, calcitriol increased the expression of mRNA for CYP24A1 but not mRNA for any bone-related or calcification-related genes. Gene expression in aortas in vivo was not altered by doses of calcitriol that promote calcification. Calcitriol markedly increased aortic calcification in uremic mice and this did not differ between VDR(-/-) aortic allografts and VDR(+/+) recipient aortas., Conclusions: Calcitriol promotes vascular calcification through a systemic action rather than through a direct vascular action.
- Published
- 2014
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