Vitamin D Receptor Activators Can Protect against Vascular Calcification
Open Access
- 1 August 2008
- journal article
- research article
- Published by Wolters Kluwer Health in Journal of the American Society of Nephrology
- Vol. 19 (8) , 1509-1519
- https://doi.org/10.1681/asn.2007080902
Abstract
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.Keywords
This publication has 64 references indexed in Scilit:
- The Mechanism of Phosphorus as a Cardiovascular Risk Factor in CKDJournal of the American Society of Nephrology, 2008
- Differential effects of vitamin D receptor activators on vascular calcification in uremic ratsKidney International, 2007
- Accelerated vascular calcification and relative hypoparathyroidism in incident haemodialysis diabetic patients receiving calcium bindersNephrology Dialysis Transplantation, 2006
- Parathyroid Hormone Controls Receptor Activator of NF-κB Ligand Gene Expression via a Distant Transcriptional EnhancerMolecular and Cellular Biology, 2006
- BMP Signaling Is Required for RUNX2-Dependent Induction of the Osteoblast PhenotypeJournal of Bone and Mineral Research, 2006
- Downregulation of parathyroid hormone receptor gene expression and osteoblastic dysfunction associated with skeletal resistance to parathyroid hormone in a rat model of renal failure with low turnover boneNephrology Dialysis Transplantation, 2005
- Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidismKidney International, 2003
- Atherosclerotic calcification: Relation to developmental osteogenesisThe American Journal of Cardiology, 1995
- High expression of genes for calcification-regulating proteins in human atherosclerotic plaques.Journal of Clinical Investigation, 1994
- Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committeeJournal of Bone and Mineral Research, 1987