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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Vascular Calcification: Current Genetics Underlying This Complex Phenomenon
Nonanzit Pérez-Hernández,Gad Aptilon-Duque,Ruben Blachman-Braun,Gilberto Vargas-Alarcón,Adrián Asael Rodríguez-Cortés,Shely Azrad-Daniel,Rosalinda Posadas-Sánchez,José Manuel Rodríguez-Pérez +7 more
TL;DR: Vascular calcification is a multifactorial disease; thus, its pathophysiology cannot be explained by a single specific factor, rather than by the result of the association of several genetic variants, molecular pathway interactions, and environmental factors that promote its development.
Journal ArticleDOI
Vascular calcification in ESRD: Another cloud appears in the perfect storm: but highlights a silver lining?
TL;DR: In patients with ESRD, London et al6 have convincingly demonstrated that both medial and intimal calcification portend mortality risk, and Aortic valve calcium content is the single best predictor of clinical progression in extant asymptomatic aortic stenosis.
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Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism: A Randomized Clinical Trial
Tetsuo Shoji,Shinya Nakatani,Daijiro Kabata,Katsuhito Mori,Ayumi Shintani,Hisako Yoshida,K. Takahashi,Keiko Ota,Hisako Fujii,Shinichiro Ueda,Shinichi Nishi,Tatsuya Nakatani,Minoru Yoshiyama,Kiyoshi Goto,Takayoshi Hamada,Masahito Imanishi,Eiji Ishimura,Sosuke Kagitani,Yoshikazu Kato,Yasuro Kumeda,Kiyoshi Maekawa,Takayasu Matsumura,Harumi Nagayama,Yasue Obi,Yoshiteru Ohno,Yoshinori Sai,Mayumi Sakurai,Satoshi Sasaki,Kaori Shidara,Shigeichi Shoji,Yoshihiro Tsujimoto,Kenjiro Yamakawa,Hideaki Yasuda,Shozo Yodoi,Masaaki Inaba,Masanori Emoto +35 more
TL;DR: In this article, a randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan.
Journal ArticleDOI
Regulation of the sodium-phosphate cotransporter Pit-1 and its role in vascular calcification.
TL;DR: Current evidence indicates a key role of increased phosphate uptake by VSMC for calcification, which supplies the substrate for hydroxyapatite formation and could trigger or potentiate VSMC transdiferentiation.
Journal ArticleDOI
Vascular damage in chronic kidney disease
Aquiles Jara,Sergio Mezzano +1 more
TL;DR: In this paper, the authors considered that increased inflammatory mediators and activation of the renin-angiotensin system contribute through enhanced production of reactive oxygen species, to atherogenesis in CKD.
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