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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Hyperphosphatemia is a combined function of high serum PTH and high dietary protein intake in dialysis patients
Elani Streja,Wei Ling Lau,Leanne Goldstein,John J. Sim,Miklos Z. Molnar,Allen R. Nissenson,Csaba P. Kovesdy,Csaba P. Kovesdy,Kamyar Kalantar-Zadeh,Kamyar Kalantar-Zadeh +9 more
TL;DR: It is hypothesized that the likelihood of hyperphosphatemia increases across higher serum PTH and higher normalized protein catabolic rate (nPCR) levels, a surrogate of protein intake, in maintenance hemodialysis patients.
Journal ArticleDOI
Role of osteoprotegerin and its ligands and competing receptors in atherosclerotic calcification.
Yin Tintut,Linda L. Demer +1 more
TL;DR: Two bone regulatory factors, receptor activator of NF-κB ligand (RANKL) and its soluble decoy receptor, osteoprotegerin (OPG), govern vascular calcification and may explain the phenomenon.
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Mechanical stimulation and mitogen-activated protein kinase signaling independently regulate osteogenic differentiation and mineralization by calcifying vascular cells.
TL;DR: Novel data indicate that mechanical signals regulate calcification by CVCs, and although MAPK signaling is critical to CVC osteogenic differentiation and mineralization, it is not involved directly in transduction of mechanical signals to regulate these processes under the conditions utilized in this study.
Journal ArticleDOI
Race, Mineral Homeostasis and Mortality in Patients with End-Stage Renal Disease on Dialysis
Julia J. Scialla,Rulan S. Parekh,Joseph A. Eustace,Brad C. Astor,Laura C. Plantinga,Bernard G. Jaar,Tariq Shafi,Josef Coresh,Neil R. Powe,Michal L. Melamed +9 more
TL;DR: Aberrant phosphorus homeostasis, reflected by higher phosphorus and FGF23, may be a risk factor for mortality in patients initiating hemodialysis, particularly among African Americans.
Journal ArticleDOI
Current and potential therapeutic strategies for the management of vascular calcification in patients with chronic kidney disease including those on dialysis
Irene Ruderman,Irene Ruderman,Stephen G Holt,Stephen G Holt,Tim D. Hewitson,Tim D. Hewitson,Edward R Smith,Edward R Smith,Nigel D Toussaint,Nigel D Toussaint +9 more
TL;DR: Current treatment strategies and therapeutic targets for the future management of VC in patients with CKD include magnesium and vitamin K supplementation and other therapeutic targets include crystallization inhibitors, ligand trap for activin receptors and BMP‐7.
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