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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Effects of a High-Protein Diet on Regulation of Phosphorus Homeostasis
Robin A. Kremsdorf,Andrew N. Hoofnagle,Mario Kratz,Mario Kratz,David S. Weigle,Holly S. Callahan,Jonathan Q. Purnell,Angela Horgan,Ian H. de Boer,Bryan Kestenbaum +9 more
TL;DR: Among healthy people, an approximate 33% increase in dietary phosphorus after institution of a high-protein diet does not cause large changes in measured concentrations of phosphorus regulatory hormones.
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Republished paper: Arterial stiffness in chronic kidney disease: causes and consequences
TL;DR: The mechanisms underlying increased arterial stiffness in chronic kidney disease are undoubtedly complex, but an understanding is paramount to enable the development of novel therapeutic strategies to prevent or reverse this pathophysiology and therefore reduce the cardiovascular disease burden in this high-risk cohort.
Journal ArticleDOI
The calcimimetic calindol prevents high phosphate-induced vascular calcification by upregulating matrix GLA protein.
TL;DR: It is demonstrated that the calcimimetic calindol prevents high Pi-induced VC by affecting osteoblastic differentiation in vitro, probably due to its stimulatory role on the calcium-sensing receptor, leading to an increase in the synthesis of MGP by VSMCs.
Journal ArticleDOI
Phospholipase D: A new mediator during high phosphate-induced vascular calcification associated with chronic kidney disease.
Najwa Skafi,Najwa Skafi,Dina Abdallah,Dina Abdallah,Christophe O. Soulage,Sophie Reibel,Nicolas Vitale,Eva Hamade,Wissam H. Faour,David Magne,Bassam Badran,Nader Hussein,René Buchet,Leyre Brizuela,Saida Mebarek +14 more
TL;DR: PLD, especially PLD1, promotes VC in the context of CKD and could be an important target for preventing onset or progression of VC.
Journal ArticleDOI
Effects of serum phosphorus on vascular calcification in a healthy, adult population: A systematic review.
TL;DR: While 8 out of 10 cross-sectional studies found an association in this systematic review, the topic of vascular calcification and serum phosphorus needs further study if a cause and effect relationship is to be detected.
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