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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Fluctuating plasma phosphorus level by changes in dietary phosphorus intake induces endothelial dysfunction
Eriko Watari,Yutaka Taketani,Tomoyo Kitamura,Terumi Tanaka,Hirokazu Ohminami,Maerjianghan Abuduli,Nagakatsu Harada,Hisami Yamanaka-Okumura,Hironori Yamamoto,Eiji Takeda +9 more
TL;DR: Habitual fluctuation of dietary P intake might be a cause of cardiovascular disease through endothelial dysfunction, especially in chronic kidney disease patients, and data indicate that repetitive fluctuations of plasma P caused by varying Dietary P intake can impair endothelial function via increased oxidative stress and inflammatory response.
Book ChapterDOI
Chronic Kidney Disease Mineral and Bone Disorder
TL;DR: This chapter summarizes the major aspects of the pathogenesis, clinical manifestations, histologic features, and therapeutic interventions currently used in the management of CKD-MBD, a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism.
Vascular calcification in dialysis patients.
TL;DR: In this paper, the authors examined the complex interplay between calcium, phosphate, vitamin D and parathyroid hormone (PTH) in patients with chronic kidney disease (CKD), and found that vitamin D has other important metabolic effects apart from this, and may confer survival advantages to patients with CKD.
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Application of a Novel CT-Based Iliac Artery Calcification Scoring System for Predicting Renal Transplant Outcomes.
Bradley Davis,Daniele Marin,Lynne M. Hurwitz,James Ronald,Matthew J. Ellis,Kadiyala V. Ravindra,Bradley H. Collins,Charles Y. Kim +7 more
TL;DR: Routine pretransplant CT for calcification scoring in patients of advanced age or those with diabetes mellitus may enable selection of the optimal artery for anastomosis to optimize outcomes.
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Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric Oxyhydroxide
TL;DR: Sucroferric oxyhydroxide offers a new option for the treatment of hyperphosphataemia, with a high phosphate-binding capacity, minimal iron release, and low potential for iron accumulation and toxicity.
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