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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Is serum phosphorus control related to parathyroid hormone control in dialysis patients with secondary hyperparathyroidism
TL;DR: This post hoc analysis of data from an earlier interventional study found that control of serum P in dialysis patients was better when serum PTH levels were lowered effectively, regardless of treatment received.
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Hyperphosphatemia and hs-CRP Initiate the Coronary Artery Calcification in Peritoneal Dialysis Patients.
TL;DR: Hyperphosphatemia and hs-CRP were the independent risk factors for CAC initiation in PD patients, and potential clinical strategies to prevent the initiation of CAC inPD patients were suggested.
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Management of hyperphosphatemia in patients with end-stage renal disease: focus on lanthanum carbonate
TL;DR: Clinical studies now document the absence of toxic effects of lanthanum for up to 6 years of follow-up, and no aluminium-like toxicity is observed since the bioavailability of Lanthanum is extremely low and its metabolism differs from that of aluminium.
Journal ArticleDOI
Heme-Mediated Activation of the Nrf2/HO-1 Axis Attenuates Calcification of Valve Interstitial Cells.
TL;DR: It is suggested that heme-mediated activation of the Nrf2/HO-1 pathway inhibits the calcification of VICs, a heart disease characterized by the progressive fibro-calcific remodeling of the aortic valves.
Journal ArticleDOI
Survival-Related Autophagic Activity Versus Procalcific Death in Cultured Aortic Valve Interstitial Cells Treated With Critical Normophosphatemic-Like Phosphate Concentrations.
Antonella Bonetti,Alberto Della Mora,Magali Contin,Giorgia Gregoraci,Franco Tubaro,Maurizio Marchini,Fulvia Ortolani +6 more
TL;DR: Fates of cultured AVICs were crucially driven by Pi concentration, suggesting that serum Pi levels just below the upper limit of normophosphatemia in humans may represent a critical watershed between macroautophagy-associated cell restoring and procalcific cell death.
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