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Publication : Role of local versus systemic vitamin D receptors in vascular calcification.

First Author  Lomashvili KA Year  2014
Journal  Arterioscler Thromb Vasc Biol Volume  34
Issue  1 Pages  146-51
PubMed ID  24202304 Mgi Jnum  J:222831
Mgi Id  MGI:5645646 Doi  10.1161/ATVBAHA.113.302525
Citation  Lomashvili KA, et al. (2014) Role of local versus systemic vitamin D receptors in vascular calcification. Arterioscler Thromb Vasc Biol 34(1):146-51
abstractText  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.
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