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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Nonphosphate-binding effects of sevelamer--are they of clinical relevance?
TL;DR: The role of phosphate binders may be more complex than initially anticipated and not limited to the extra calcium load, and may have a number of additional nonphosphate‐lowering actions.
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TL;DR: A comparative effectiveness study—a direct comparison of different phosphate binders in real-world settings to determine the most effective treatment based on individual characteristics—is a priority in clinical research in patients with ESRD.
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Elevated parathyroid hormone predicts mortality in dialysis patients undergoing valve surgery.
Huan Yan,Jyotirmay Sharma,Collin J. Weber,Robert A. Guyton,Sebastian D. Perez,Vinod H. Thourani +5 more
TL;DR: Preoperative PTH level ≥ 200 pg/mL is predictive of increased mortality after valve surgery among dialysis patients, and hyperparathyroidism should be investigated further as a possible modifiable risk factor for postoperative mortality in this high-risk patient cohort.
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Excessive dietary phosphorus intake impairs endothelial function in young healthy men: a time- and dose-dependent study
Tamae Nishi,Emi Shuto,Mariko Ogawa,Miho Ohya,Misaki Nakanishi,Masashi Masuda,Misaki Katsumoto,Hisami Yamanaka-Okumura,Tohru Sakai,Eiji Takeda,Hiroshi Sakaue,Yutaka Taketani +11 more
TL;DR: The results indicate that excessive dietary P intake can acutely impair endothelial function in healthy people.
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