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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Journal ArticleDOI
Phenotypic Modulation of Cultured Primary Human Aortic Vascular Smooth Muscle Cells by Uremic Serum.
Violeta Cazaña-Pérez,Pilar Cidad,Javier Donate-Correa,Ernesto Martín-Núñez,José R. López-López,M. Teresa Pérez-García,Teresa Giraldez,Juan F. Navarro-González,Diego Alvarez de la Rosa +8 more
TL;DR: Primary cultures of human VSMC treated with serum from uremic patients provides a more informative model for the study of vascular calcification secondary to CKD, according to fundamental differences in osteochondrogenic marker expression and alkaline phosphatase induction.
Book ChapterDOI
Extracellular phosphate as a signaling molecule.
TL;DR: This chapter will review the findings regarding the regulation of various cellular functions by extracellular Pi, and also discuss the current concept on the mechanism for Pi-sensing in mammalian cells.
Journal ArticleDOI
Oral phosphate binders: history and prospects.
TL;DR: Metal salt type oral phosphate binder is the most classical type of oral phosphate binders that includes aluminum hydroxide gel and lanthanum carbonate and effectively adsorb phosphate ions, however, have a potential risk for accumulation and intoxication.
Journal ArticleDOI
Laminaria japonica Polysaccharide Inhibits Vascular Calcification via Preventing Osteoblastic Differentiation of Vascular Smooth Muscle Cells
TL;DR: Results indicated that L JP61A ameliorated VC both in vivo and in vitro via preventing osteoblastic differentiation of VSMC, suggesting LJP61A might be a potential therapeutic agent for VC in CRF patients.
Journal ArticleDOI
Vascular calcification in chronic kidney disease: usefulness of a marker of vascular damage.
Antonio Bellasi,Paolo Raggi +1 more
TL;DR: The strengths and limitations of the most common noninvasive techniques employed to imageVC are reviewed and the prognostic implications of VC are reviewed.
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