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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Daily peritoneal administration of sodium pyrophosphate in a dialysis solution prevents the development of vascular calcification in a mouse model of uraemia
Bruce L. Riser,Fellype C. Barreto,Raja Rezg,Paul W. Valaitis,Chyung Cook,Jeff White,Jerome H. Gass,Julien Maizel,Loïc Louvet,Tilman B. Drüeke,Clifford J. Holmes,Ziad A. Massy +11 more
TL;DR: Findings suggest potential for PPi, administered during PD, to prevent the development of VC and to potentially extend the life of ESRD patients.
Journal ArticleDOI
Fetuin-A-containing calciprotein particles in mineral trafficking and vascular disease
TL;DR: Mineral trafficking is a loose term used to describe the movements of calcium salts around the body, and new insights into these pathways may explain some of the problems of previous models of bone mineral disease in renal failure and point to potential future therapeutic strategies.
Journal ArticleDOI
No independent association of serum phosphorus with risk for death or progression to end-stage renal disease in a large screen for chronic kidney disease
Rajnish Mehrotra,Carmen A. Peralta,Shu Cheng Chen,Suying Li,Michael C. Sachs,Anuja Shah,Keith C. Norris,Georges Saab,Adam Whaley-Connell,Bryan Kestenbaum,Peter A. McCullough +10 more
TL;DR: In the largest cohort of individuals with early-stage CKD to date, an independent association of serum phosphorus with risk for death or progression to ESRD is not validated.
Journal ArticleDOI
High pretransplant parathyroid hormone levels increase the risk for graft failure after renal transplantation.
Joke I. Roodnat,Eveline A. F. J. van Gurp,Paul G.H. Mulder,Teun van Gelder,Yolanda B. de Rijke,Wouter W. de Herder,Judith A. Kal-van Gestel,H. A. P. Pols,Jan N. M. IJzermans,Willem Weimar +9 more
TL;DR: Serum PTH levels have an independent influence on the risk for graft failure censored for death and efforts to improve calcium-phosphate-PTH homeostasis in patients on the waiting list for renal transplantation should be encouraged also to improve graft survival.
Journal ArticleDOI
Activation of Nrf2 by dimethyl fumarate improves vascular calcification.
Chae-Myeong Ha,Sungmi Park,Young-Keun Choi,Ji-Yun Jeong,Chang Joo Oh,Kwi-Hyun Bae,Sun Joo Lee,Ji-Hyun Kim,Keun-Gyu Park,Do Youn Jun,Inkyu Lee +10 more
TL;DR: The data support that DMF stimulates Nrf2 activity to attenuate hyperphosphatamia in vitro or Vitamin D3-induced in vivo vascular calcification, which would be a beneficial effect on vascular diseases induced by oxidative stress such as vascular calcifying.
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Coronary-Artery Calcification in Young Adults with End-Stage Renal Disease Who Are Undergoing Dialysis
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing
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