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
Effects of dietary phosphates from organic and inorganic sources on parameters of phosphorus homeostasis in healthy adult dogs.
TL;DR: In this article, the effects of different P sources on concentration and post-prandial kinetics of selected parameters of P homeostasis in dogs were examined and the results indicated distinct disturbances of Ca and P metabolism, in contrast to organic sources.
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Methods in mouse atherosclerosis
Vicente Andrés,Beatriz Dorado +1 more
TL;DR: This chapter reviews several mouse models of atherosclerosis progression and regression as well as the role of immune cells in disease progression and the genetics of murine atherogenesis.
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Phosphate control in peritoneal dialysis
Mario Cozzolino,Andrea Stucchi,Maria Antonietta Rizzo,Irene Brenna,Francesca Elli,Paola Ciceri,Jordi Bover,Daniele Cusi,Maurizio Gallieni +8 more
TL;DR: In patients with CKD stage 5 on dialysis, therapeutic approaches to reduce serum P levels should include restriction of dietary phosphate intake, optimal dialysis treatment, and use of P binders.
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Risk factors for calciphylaxis in Chinese hemodialysis patients: a matched case-control study.
TL;DR: In this article, a lack of data from kidney dialysis patients was identified as a risk factor for calciphylaxis, a rare but potentially fatal disease commonly occurred in kidney patients.
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Osteoporosis and cardiovascular disease: lessons from chronic kidney disease.
TL;DR: The mechanisms of CKD induced cardiovascular risk provide valuable insight into the relationship between cardiovascular disease and osteoporosis, and they are reviewed here.
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