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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Regulation of Vascular Calcification by Growth Hormone-Releasing Hormone and Its Agonists.
Jian Shen,Ning Zhang,Yi Nuo Lin,Ping Ping Xiang,Xian Bao Liu,Peng Fei Shan,Xin Yang Hu,Wei Zhu,Yao Liang Tang,Keith A. Webster,Renzhi Cai,Andrew V. Schally,Jian-an Wang,Hong Yu +13 more
TL;DR: GHRH-A controls osteogenesis in smooth muscle cells by targeting cross talk between protein kinase A and nuclear factor &kgr;B and through the suppression of reactive oxygen species production that induces the Runx2 gene and alkaline phosphatase osteogenesis program.
Journal ArticleDOI
Impaired Response of FGF-23 to Oral Phosphate in Patients with Type 2 Diabetes: A Possible Mechanism of Atherosclerosis
Koichiro Yoda,Yasuo Imanishi,Maki Yoda,Takashi Mishima,Mitsuru Ichii,Shinsuke Yamada,Katsuhito Mori,Masanori Emoto,Masaaki Inaba +8 more
TL;DR: Results show that increases of serum FGF-23 and PTH in response to Pi stimulation are impaired in type 2 DM and that serum Pi is significantly increased thereafter, which may be a mechanism underlying advanced atherosclerosis in type 1 DM.
Journal ArticleDOI
Klotho: A Major Shareholder in Vascular Aging Enterprises
TL;DR: Emerging data have provided fundamental rationale for Klotho-based therapeutic intervention for vascular diseases and multiple other potential indications and the identification of α-Klotho, a remarkable protein that confers powerful anti-aging properties has stimulated significant interest.
Journal ArticleDOI
Klotho in cardiovascular disease: Current and future perspectives
Javier Donate-Correa,Ernesto Martín-Núñez,Carmen Mora-Fernández,Mercedes Muros-de-Fuentes,Nayra Pérez-Delgado,Juan F. Navarro-González +5 more
TL;DR: Protein Klotho, beyond its role as a regulator of the phosphatemia, is also involved in the maintaining of the cardiovascular health, being associated its alterations with the development of cardiovascular damage and increased morbi-mortality.
Journal ArticleDOI
Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells
Gergely Becs,Abolfazl Zarjou,Anupam Agarwal,Katalin Éva Kovács,Ádám Becs,Mónika Nyitrai,Enikő Balogh,Emese Bányai,John W. Eaton,Paolo Arosio,Maura Poli,Viktória Jeney,Viktória Jeney,József Balla,József Balla,György Balla +15 more
TL;DR: Pharmacological induction of heavy chain ferritin by 3H‐1,2‐Dithiole‐3‐thione was able to inhibit the SMC transition into osteoblast‐like cells and calcification of extracellular matrix.
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