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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Ethanol increases phosphate-mediated mineralization and osteoblastic transformation of vascular smooth muscle cells.
Melinda Oros,Erzsébet Zavaczki,Csaba Vadasz,Csaba Vadasz,Viktória Jeney,Arpad Tosaki,Istvan Lekli,György Balla,György Balla,Laszlo Nagy,József Balla,József Balla +11 more
TL;DR: It is concluded that ethanol enhances Pi‐mediated human vascular smooth muscle calcification and transition of these cells into osteoblast‐like cells, and is associated with greater calcification in coronary arteries.
Journal ArticleDOI
Beyond phosphate—role of uraemic toxins in cardiovascular calcification
TL;DR: Evidence is accumulating that soft tissue calcification is not only a passive process involving calcium and phosphate precipitation due to low ion solubility in serum, but also an active process involving numerous players and the complex interaction between active and passive processes guarantees the prevention of soft tissue calcium phosphate deposition under physiological circumstances.
Journal ArticleDOI
Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications.
Laura Salanova Villanueva,Carmen Sánchez González,José Antonio Sánchez Tomero,Abelardo Aguilera,Esther Ortega Junco +4 more
TL;DR: The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known but the newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease.
Journal ArticleDOI
Coronary calcification in patients with end-stage renal disease: a novel endocrine disorder?
TL;DR: Despite the evident effectiveness of both traditional and innovative remedies in the management of metabolic and electrolytic abnormalities of patients with end-stage renal disease, an individualized intervention based on etiopathogenesis is really required.
Journal ArticleDOI
Oral phosphorus supplementation secondarily increases circulating fibroblast growth factor 23 levels at least partially via stimulation of parathyroid hormone secretion.
TL;DR: The results suggest that oral phosphorus supplementation secondarily increases circulating FGF23 levels at least partially by stimulation of PTH secretion.
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