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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Novel treatment strategies for chronic kidney disease: insights from the animal kingdom
Peter Stenvinkel,Johanna Painer,Makoto Kuro-o,Miguel A. Lanaspa,Walter Arnold,Thomas Ruf,Paul G. Shiels,Richard J. Johnson +7 more
TL;DR: Improved understanding of the susceptibility and protective mechanisms of these animals and others could provide insights into novel strategies to prevent and treat several human diseases, such as CKD and ageing-associated complications.
Journal ArticleDOI
Lanthanum: a safe phosphate binder.
TL;DR: In this paper, the metabolism of lanthanum carbonate and its effects in bone, liver and brain are discussed, with no signs of direct bone toxicity yet observed in rats or humans.
Journal ArticleDOI
Hydrogen sulfide inhibits the calcification and osteoblastic differentiation of vascular smooth muscle cells
Erzsébet Zavaczki,Viktória Jeney,Viktória Jeney,Anupam Agarwal,Abolfazl Zarjou,Abolfazl Zarjou,Melinda Oros,Mónika Katkó,Zsuzsa Varga,György Balla,György Balla,József Balla,József Balla +12 more
TL;DR: H2S is a potent inhibitor of phosphate-induced calcification and osteoblastic differentiation of VSMC, and this mechanism might contribute to accelerated vascular calcification in chronic kidney disease.
Journal ArticleDOI
Treatment of Hemodialysis-Associated Adynamic Bone Disease with Teriparatide (PTH1-34): A Pilot Study.
TL;DR: Teriparatide therapy might improve low BMD in hemodialysis patients with ABD, and calculated monthly changes in BMD improved significantly in both the lumbar spine and femoral neck, compared to pretreatment values.
Journal ArticleDOI
Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism
Masahide Mizobuchi,Hiroaki Ogata,Ikuji Hatamura,Fumihiko Koiwa,Fumie Saji,Kazuhiro Shiizaki,Shigeo Negi,Eriko Kinugasa,Akira Ooshima,Shozo Koshikawa,Tadao Akizawa +10 more
TL;DR: Results suggest that medial layer vascular calcification in uraemic rats with severe hyperphosphataemia and SHPT may be caused in part by Cbfa1 and Pit-1.
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