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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Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation
Yuichi Takashi,Yuichi Takashi,Hidetaka Kosako,Shun Sawatsubashi,Yuka Kinoshita,Nobuaki Ito,Maria K. Tsoumpra,Masaomi Nangaku,Masahiro Abe,Munehide Matsuhisa,Shigeaki Kato,Toshio Matsumoto,Seiji Fukumoto +12 more
TL;DR: The present study elucidates a Pi-sensing mechanism in the control of serum FGF23 levels and provides a molecular basis for a better understanding of hypo- or hyperphosphatemic diseases.
Journal ArticleDOI
Endochondral bone formation is involved in media calcification in rats and in men
TL;DR: The presence of chondrocytes in association with calcification of the media in aortas of rats with CRF mimics endochondral bone formation and is demonstrated by the chondrogenic conversion of medial smooth muscle cells in the human aorta.
Journal ArticleDOI
Long-Term Efficacy and Tolerability of Lanthanum Carbonate: Results from a 3-Year Study
Alastair J. Hutchison,Bart Maes,J Vanwalleghem,Gernot Asmus,Elfatih Mohamed,Roland Schmieder,Wolfgang Backs,Rene Jamar,Andre Vosskühler +8 more
TL;DR: Lanthanum carbonate maintains effectiveness with continued tolerability for up to 3 years, and was well tolerated; adverse events were mild/moderate and mainly gastrointestinal.
Journal ArticleDOI
The case against calcium-based phosphate binders.
Sharon M. Moe,Glenn M. Chertow +1 more
TL;DR: Calcium-based phosphate binders should be avoided in many, if not most, patients who are undergoing dialysis, because of the compelling biologic plausibility that hyperphosphatemia and excess exogenous calcium administration can accelerate vascular calcification.
Journal ArticleDOI
Transglutaminase 2 Is Central to Induction of the Arterial Calcification Program by Smooth Muscle Cells
TL;DR: The results suggest that TG2 release in injured arteries is critical for programming chondro–osseous SMC differentiation and calcification in response to increased Pi and bone morphogenetic protein-2.
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