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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Calcium-phosphate levels and cardiovascular disease in community-dwelling adults: the Atherosclerosis Risk in Communities (ARIC) Study.
TL;DR: Although calcium, phosphate, and calcium-phosphate product levels exhibit complex associations with traditional cardiovascular risk factors and outcomes, they may be potentially modifiable risk factors for stroke and death in community-dwelling adults.
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Coronary Artery Calcification and Risk of Cardiovascular Disease and Death Among Patients With Chronic Kidney Disease
Jing Chen,Matthew J. Budoff,Muredach P. Reilly,Wei Yang,Sylvia E. Rosas,Mahboob Rahman,Xiaoming Zhang,Jason Roy,Eva Lustigova,Lisa Nessel,Virginia Ford,Dominic S. Raj,Anna C. Porter,Elsayed Z. Soliman,Jackson T. Wright,Myles Wolf,Jiang He +16 more
TL;DR: CAC improves risk prediction for cardiovascular disease, myocardial infarction, and heart failure over use of established and novel cardiovascular disease risk factors among patients with CKD; however, the changes in the C statistic are small.
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Phosphate transporters: a tale of two solute carrier families.
TL;DR: This review focuses on recent advances in the characterization of the transport kinetics, structure-function relationships, and physiological implications of having two distinct Na+/P(i) cotransporter families.
Journal ArticleDOI
The Mechanism of Phosphorus as a Cardiovascular Risk Factor in CKD
Suresh Mathew,Kimberly S. Tustison,Toshifumi Sugatani,Lala R. Chaudhary,Leonard Rifas,Keith A. Hruska +5 more
TL;DR: It is concluded that, in chronic kidney disease, hyperphosphatemia stimulates an osteoblastic transcriptional program in the vasculature, which is mediated by osterix activation in cells of the vascular tunica media and neointima.
Journal ArticleDOI
Vascular smooth muscle cell phenotypic plasticity and the regulation of vascular calcification
TL;DR: The osteo/chondrocytic conversion of VSMCs and the association of this phenotype with vascular calcification is a paradigm for how inappropriate differentiation can influence disease processes.
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