Vitamin D receptor activators can protect against vascular calcification.
An apparent conflict exists between observational studies that suggest that vitamin D receptor (VDR) activators provide a survival advantage for patients with ESRD and other studies that suggest that they cause vascular calcification. In an effort to explain this discrepancy, we studied the effects of the VDR activators calcitriol and paricalcitol on aortic calcification in a mouse model of chronic kidney disease (CKD)-stimulated atherosclerotic cardiovascular mineralization. At dosages sufficient to correct secondary hyperparathyroidism, calcitriol and paricalcitol were protective against aortic calcification, but higher dosages stimulated aortic calcification. At protective dosages, the VDR activators reduced osteoblastic gene expression in the aorta, which is normally increased in CKD, perhaps explaining this inhibition of aortic calcification. Interpreting the results obtained using this model, however, is complicated by the adynamic bone disorder; both calcitriol and paricalcitol stimulated osteoblast surfaces and rates of bone formation. Therefore, the skeletal actions of the VDR activators may have contributed to their protection against aortic calcification. We conclude that low, clinically relevant dosages of calcitriol and paricalcitol may protect against CKD-stimulated vascular calcification.
Mathew
Suresh
S
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Lund
Richard J
RJ
Chaudhary
Lala R
LR
Geurs
Theresa
T
Hruska
Keith A
KA
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001018:Aortic Diseases / Q000209:etiology / Q000517:prevention & control; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001849:Bone Diseases, Endocrine / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002114:Calcinosis / Q000209:etiology / Q000517:prevention & control*; D002117:Calcitriol / Q000008:administration & dosage*; D002118:Calcium / Q000097:blood; D004041:Dietary Fats / Q000009:adverse effects; D004872:Ergocalciferols / Q000008:administration & dosage*; D005260:Female; D005269:Femur / Q000187:drug effects / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000187:drug effects; D010758:Phosphorus / Q000097:blood; D018167:Receptors, Calcitriol / Q000819:agonists
D050071:Bone Density Conservation Agents; D004041:Dietary Fats; D004872:Ergocalciferols; D018167:Receptors, Calcitriol; D010758:Phosphorus; C084656:paricalcitol; D002117:Calcitriol; D002118:Calcium