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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Association of mineral metabolism with an increase in cellular adhesion molecules: another link to cardiovascular risk in maintenance haemodialysis?
Mustafa Arici,Serkan Kahraman,Gultekin Genctoy,Bulent Altun,Umut Kalyoncu,Aytekin Oto,Serafettin Kirazli,Yunus Erdem,Ünal Yasavul,Cetin Turgan +9 more
TL;DR: Findings suggest that in stable haemodialysis patients abnormal bone mineral metabolism was associated with increased soluble adhesion molecules, which may favour the development of cardiovascular changes and contribute to high cardiovascular morbidity and mortality in patients with abnormal mineral metabolism.
Journal ArticleDOI
Active vitamin D and accelerated progression of aortic stiffness in hemodialysis patients: a longitudinal observational study
C. Fortier,Fabrice Mac-Way,Sacha A. De Serres,Karine Marquis,Pierre Douville,Simon Desmeules,Richard Larivière,Mohsen Agharazii,Mohsen Agharazii +8 more
TL;DR: It is suggested that the vascular safety of active vitamin D posology may need to be specifically addressed in the treatment of chronic kidney disease-related bone mineral disorder.
Journal ArticleDOI
Cardiac calcium evaluation in hemodialysis patients with multisection spiral computed tomography.
G. Splendiani,Massimo Morosetti,Micaela Manni,L. Jankovic,Alessandro Naticchia,Antonio Sturniolo,T. Tullio,Alessandro Balducci,Giorgio Coen +8 more
TL;DR: Risk factors for cardiac calcification are mainly age, degree of hyperparathyroidism, increased CaxP and serum calcium levels, and a control of calcium phosphate parameters in hemodialysis patients seems to be mandatory to avoid increased severity of coronary artery disease.
Journal ArticleDOI
Diagnostic Workup for Disorders of Bone and Mineral Metabolism in Patients with Chronic Kidney Disease in the Era of KDIGO Guidelines
TL;DR: A summary will be provided of the most important findings of KDIGO guidelines regarding the diagnostic workup and clinical monitoring of CKD-MBD patients.
Journal ArticleDOI
Autophagy protects kidney from phosphate-induced mitochondrial injury.
Ryuta Fujimura,Takeshi Yamamoto,Yoshitsugu Takabatake,Atsushi Takahashi,Tomoko Namba-Hamano,Satoshi Minami,Shinsuke Sakai,Jun Matsuda,Atsushi Hesaka,Hiroaki Yonishi,Jun Nakamura,Isao Matsui,Taiji Matsusaka,Fumio Niimura,Motoko Yanagita,Yoshitaka Isaka +15 more
TL;DR: In this paper, the role of autophagy in kidney proximal tubular cells (PTECs) during phosphate overload was studied, and it was shown that high phosphate activates mitophagy to degrade increasing substrate.
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