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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New developments in hyperphosphatemia management.
TL;DR: Management of hyperphosphatemia is a critical issue in the care of patients with renal failure and has the potential to decrease risk for CVD, particularly when instituted with appropriate measures to control other “traditional” cardiovascular risk factors.
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Uremic Cardiomyopathy: A New Piece in the Chronic Kidney Disease-Mineral and Bone Disorder Puzzle
TL;DR: The data suggest that the uremic cardiomyopathy can be considered a new piece in the CKD-DMO puzzle by exploring the recent data that identify the triad of hyperphosphatemia, high FGF23 levels and αKlotho deficiency as playing a central role on it.
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The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD
Rakesh Malhotra,Ronit Katz,Andrew N. Hoofnagle,Andrew G. Bostom,Dena E. Rifkin,Dena E. Rifkin,Ruth McBride,Jeffrey L. Probstfield,Geoffrey A. Block,Joachim H. Ix,Joachim H. Ix +10 more
TL;DR: The use of niacin over 3 years lowered serum phosphorous concentrations but did not affect other markers of mineral metabolism in participants with CKD.
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Fibroblast Growth Factor-23-A Potential Uremic Toxin.
TL;DR: The best way to normalize plasma FGF23 in maintenance hemodialysis patients is restoring kidney function by successful kidney transplantation, and anti-FGF23 antibodies have also recently been developed to inhibit the action of F GF23 in target organs.
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Transcriptional Programming in Arteriosclerotic Disease: A Multifaceted Function of the Runx2 (Runt-Related Transcription Factor 2).
TL;DR: The regulation of this key osteogenic transcription factor and its new perspectives in the vasculature will provide novel insights into the transcriptional regulation of vascular smooth muscle cell phenotype switch, reprograming, and vascular inflammation that promote the pathogenesis of arteriosclerosis.
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing
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