Phosphate Regulation of Vascular Smooth Muscle Cell Calcification
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- 29 September 2000
- journal article
- other
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 87 (7), E10-7
- https://doi.org/10.1161/01.res.87.7.e10
Abstract
—Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralization in vitro was examined. HSMCs cultured in media containing normal physiological levels of inorganic phosphate (1.4 mmol/L) did not mineralize. In contrast, HSMCs cultured in media containing phosphate levels comparable to those seen in hyperphosphatemic individuals (>1.4 mmol/L) showed dose-dependent increases in mineral deposition. Mechanistic studies revealed that elevated phosphate treatment of HSMCs also enhanced the expression of the osteoblastic differentiation markers osteocalcin and Cbfa-1. The effects of elevated phosphate on HSMCs were mediated by a sodium-dependent phosphate cotransporter (NPC), as indicated by the ability of the specific NPC inhibitor phosphonoformic acid, to dose dependently inhibit phosphate-induced calcium deposition as well as osteocalcin and Cbfa-1 gene expression. With the use of polymerase chain reaction and Northern blot analyses, the NPC in HSMCs was identified as Pit-1 (Glvr-1), a member of the novel type III NPCs. These data suggest that elevated phosphate may directly stimulate HSMCs to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. The full text of this article is available at http://www.circresaha.org.Keywords
This publication has 29 references indexed in Scilit:
- Null Mutation in the Desmin Gene Gives Rise to a CardiomyopathyJournal of Molecular and Cellular Cardiology, 1997
- Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA proteinNature, 1997
- Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitroJournal of Bone and Mineral Research, 1996
- Use of phosphonocarboxylic acids as inhibitors of sodium-phosphate cotransportGeneral Pharmacology: The Vascular System, 1996
- The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro.JCI Insight, 1995
- Calcification of valved aortic allografts in rats: Effects of age, crosslinking, and inhibitorsJournal of Biomedical Materials Research, 1995
- Diffuse calcification in human coronary arteries. Association of osteopontin with atherosclerosis.JCI Insight, 1994
- TGF-beta 1 and 25-hydroxycholesterol stimulate osteoblast-like vascular cells to calcify.JCI Insight, 1994
- Calcium — a Neglected Key Factor in Arteriosclerosis. The Pathogenetic Role of Arterial Calcium Overload and Its Prevention by Calcium AntagonistsAnnals of Medicine, 1991
- Significance of calcification of the coronary arteriesThe American Journal of Cardiology, 1970