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
Citations
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Phosphate binders in CKD: chalking out the differences.
Lesley Rees,Rukshana Shroff +1 more
TL;DR: The role of phosphate as a uraemic toxin and the advantages and disadvantages of the currently available phosphate binders are discussed.
Journal ArticleDOI
Vitamin-D receptor agonist calcitriol reduces calcification in vitro through selective upregulation of SLC20A2 but not SLC20A1 or XPR1.
TL;DR: It is suggested that vitamin D might be used to regulate SLC20A2 gene expression, as well as reduce brain calcification which occurs in Fahr’s disease and normal aging.
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Potential Role of H-Ferritin in Mitigating Valvular Mineralization.
Katalin Éva Sikura,Katalin Éva Sikura,László Potor,László Potor,Tamás Szerafin,Abolfazl Zarjou,Anupam Agarwal,Paolo Arosio,Maura Poli,Zoltán Hendrik,Gábor Méhes,Melinda Oros,Melinda Oros,Niké Posta,Niké Posta,Lívia Beke,Ibolya Fürtös,György Balla,György Balla,József Balla,József Balla +20 more
TL;DR: The results indicate that H-ferritin is a stratagem in mitigating valvular mineralization/osteoblastic differentiation and corroborates the essential role of ferritin/ferroxidase via attenuating inflammation in calcific aortic valve disease.
Journal ArticleDOI
Paricalcitol [19-nor-1,25-(OH)2D2] in the treatment of experimental renal bone disease.
Jarkko Jokihaara,Ilkka Pörsti,Ilari Pajamäki,Tuomo Vuohelainen,Pasi Jolma,Peeter Kööbi,Jarkko Kalliovalkama,Onni Niemelä,Pekka Kannus,Harri Sievänen,Teppo L. N. Järvinen +10 more
TL;DR: It is shown that paricalcitol also ameliorates the renal insufficiency‐induced loss of bone mineral and the mechanical competence of bone.
Journal ArticleDOI
The impact of calcimimetics on mineral metabolism and secondary hyperparathyroidism in end-stage renal disease.
TL;DR: Recently completed phase 2 clinical trials with the second-generation calcimimetic agent cinacalcet HCl confirm that this agent represents a safe and effective novel therapeutic agent which has the potential to dramatically alter the treatment and complications associated with secondary hyperparathyroidism in patients on dialysis.
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