Phosphate regulation of vascular smooth muscle cell calcification.
Shuichi Jono,Marc D. McKee,Charles E. Murry,Atsushi Shioi,Yoshiki Nishizawa,Katsuhito Mori,Hirotoshi Morii,Cecilia M. Giachelli +7 more
TLDR
It is suggested 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.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.read more
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Abstract 3751: Phosphorus Levels are Associated with Subclinical Atherosclerosis in the General Population
Stephen Onufrak,Antonio Bellasi,Leslee J. Shaw,Charles A. Herzog,Francesca Cardarelli,Peter W.F. Wilson,Viola Vaccarino,Paolo Raggi +7 more
TL;DR: In a population-based cohort of subjects free of overt cardiovascular and renal disease serum phosphorus was positively associated with cIMT independent of traditional risk factors for atherosclerosis and eGFR in men but not in women.
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TL;DR: This Review summarizes the mechanisms of ectopic calcification processes in the cardiovascular system, with an emphasis on emerging knowledge obtained from advances in imaging methods, experimental models and multiomics-generated big data.
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Mild hyperphosphatemia and mortality in hemodialysis patients.
Alberto Rodríguez-Benot,Alejandro Martin-Malo,M. Antonia Alvarez-Lara,Mariano Rodriguez,Pedro Aljama +4 more
TL;DR: A serum phosphate level greater than 5.0 mg/dL (>1.61 mmol/L) is independently associated with an increased risk for death in HD patients.
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The Effects of Sevelamer Hydrochloride and Calcium Carbonate on Kidney Calcification in Uremic Rats
Mario Cozzolino,Adriana Dusso,Helen Liapis,Jane Finch,Yan Lu,Steven K. Burke,Eduardo Slatopolsky +6 more
TL;DR: In experimental CRF in rats, despite a similar control of serum P and SH, sevelamer is more effective than CaCO(3) in preventing renal Ca deposition and tubulointerstitial fibrosis, including better preservation of renal function.
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Direct Effects of Phosphate on Vascular Cell Function
TL;DR: The current knowledge about phosphate-induced changes in the vascular wall is reviewed and the sodium-phosphate cotransporter PiT-1 is reviewed for its role in smooth muscle cell phenotype change and apoptosis.
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