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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Skeletonized coronary arteries: pathophysiological and clinical aspects of vascular calcification
Carlos V. Serrano,Marcelo Oranges,Vitor Ottoboni Brunaldi,Alexandre de Matos Soeiro,Tatiana Andreucci Torres,Jose C. Nicolau,José Antonio Franchini Ramires +6 more
TL;DR: The role of calcification in coronary artery disease is gaining importance, both in research studies and in clinical application, and a number of diagnostic imaging methods have been developed in recent years, but their performance needs to be improved.
Journal ArticleDOI
A randomized, double-blind, placebo-controlled trial of calcium acetate on serum phosphorus concentrations in patients with advanced non-dialysis-dependent chronic kidney disease
Wajeh Y. Qunibi,Wolfgang C. Winkelmayer,Richard Solomon,Moustafa Moustafa,Paul D. Kessler,Chiang Hong Ho,Jonathan Greenberg,Jose A. Diaz-Buxo +7 more
TL;DR: In CKD patients not yet on dialysis, calcium acetate was effective in reducing serum phosphorus and intact parathyroid hormone levels over a 12 week period.
Journal ArticleDOI
Serum 25-Hydroxyvitamin D Level Is Associated With Arterial Stiffness, Left Ventricle Hypertrophy, and Inflammation in Newly Diagnosed Hypertension
Osman Kuloğlu,Mustafa Gür,Taner Şeker,Gülhan Yüksel Kalkan,Durmuş Yıldıray Şahin,Ibrahim Halil Tanboga,Nermin Yıldız Koyunsever,Hazar Harbaloğlu,Caner Türkoğlu,Selahattin Akyol,Zafer Elbasan,Armağan Acele,Murat Çaylı +12 more
TL;DR: Serum 25-hyroxyvitamin D is independently related with arterial stiffness, LVH, and inflammation; however, adjustment for parathyroid hormone level or body surface area and mean blood pressure attenuate this association.
Journal ArticleDOI
Proteomic profiling of extracellular vesicles released from vascular smooth muscle cells during initiation of phosphate-induced mineralization.
Sandeep C. Chaudhary,Sana Khalid,Victoria Smethurst,Daisy Monier,James A. Mobley,Alexis Huet,James F. Conway,Dobrawa Napierala +7 more
TL;DR: Exposure of MOVAS cells to high phosphate levels stimulates the release of extracellular vesicles and changes their protein composition, which is one of the major factors contributing to vascular calcification.
Journal ArticleDOI
Phosphate Levels and Blood Pressure in Incident Hemodialysis Patients: A Longitudinal Study
Cindy Xin Huang,Laura C. Plantinga,Nancy E. Fink,Michal L. Melamed,Josef Coresh,Neil R. Powe +5 more
TL;DR: It is suggested that serum phosphate level is strongly and independently associated with blood pressure in hemodialysis patients and the effect of rigorous control of serum phosphate levels on arterial stiffness and blood pressure should be studied in clinical trials.
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