title: Role of local versus systemic vitamin D receptors in vascular calcification.
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.
  
  
  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.
authors.affiliation: From the Renal Division, Emory University School of Medicine, Atlanta, GA.
authors.forename: Koba A
authors.initials: KA
authors.lastname: Lomashvili
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Wang
authors.forename: W Charles
authors.initials: WC
authors.lastname: O'Neill
mesh_terms: D000225:Adenine; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D002117:Calcitriol / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D005819:Genetic Markers; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques; D015854:Up-Regulation; D014511:Uremia / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D061205:Vascular Calcification / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D005819:Genetic Markers; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D013250:Steroid Hydroxylases; C585550:Cyp24a1 protein, mouse; C585551:Cyp24a1 protein, rat; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; D000225:Adenine
keywords: renal failure; transplantation; vascular calcification; vitamin D