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
Citations
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Simple evaluation of aortic arch calcification by chest radiography in hemodialysis patients
Tetsuya Ogawa,Hideki Ishida,Nami Matsuda,Ayuko Fujiu,Akiko Matsuda,Kyoko Ito,Yoshitaka Ando,Kosaku Nitta +7 more
TL;DR: A simple measurement of AoACS may be useful for inoffice imaging to choose a therapeutic regimen in HD patients to assess a poor prognosis in dialysis patients.
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Vascular calcification in chronic kidney disease: Pathogenesis and clinical implication
TL;DR: Reduction of calcium load, lowering phosphate retention using non-calcium containing phosphate binders, and moderate doses of active vitamin D may attenuate progression, while Parenteral sodium thiosulfate has also been shown to delay VC progression.
Journal ArticleDOI
Arterial Stiffness: A Focus on Vascular Calcification and Its Link to Bone Mineralization.
TL;DR: The impact of the systemic and microenvironmental factors on respective intrinsic signaling pathways that promote osteogenic differentiation and calcification of vascular smooth muscle cells and osteoblasts are compared and contrasted, aiming to dissect the commonalities and distinctions that underlie the paradoxical vascular-bone mineralization disorders in aging and diseases.
Journal ArticleDOI
Phosphorus and Risk of Renal Failure in Subjects with Normal Renal Function
John J. Sim,Simran K. Bhandari,Ning Smith,Joanie Chung,In Lu A. Liu,Steven J. Jacobsen,Kamyar Kalantar-Zadeh +6 more
TL;DR: In a large, ethnically diverse cohort of non kidney disease subjects, higher serum phosphorus levels were associated with greater risk for end-stage renal disease and mortality.
Journal ArticleDOI
MicroRNAs that target Ca(2+) transporters are involved in vascular smooth muscle cell calcification.
TL;DR: The results suggest that increased expression of miRNAs may be involved in VSMC calcification by disrupting Ca2+ efflux proteins.
References
More filters
Journal ArticleDOI
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
TL;DR: Cloned cDNA encoding Osf2/Cbfa1 is identified as an osteoblast-specific transcription factor and as a regulator of osteoblasts differentiation.
Journal ArticleDOI
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Makoto Kuro-o,Matsumura Yutaka,Hiroki Aizawa,Hiroshi Kawaguchi,Tatsuo Suga,Toshihiro Utsugi,Yoshio Ohyama,Masahiko Kurabayashi,Tadashi Kaname,Eisuke Kume,Hitoshi Iwasaki,Akihiro Iida,Takako Shiraki-Iida,Satoshi Nishikawa,Ryozo Nagai,Ryozo Nagai,Yo-ichi Nabeshima +16 more
TL;DR: A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes in the mouse, and may function as part of a signalling pathway that regulates ageing in vivo and morbidity in age-related diseases.
Journal ArticleDOI
Cbfa1, a Candidate Gene for Cleidocranial Dysplasia Syndrome, Is Essential for Osteoblast Differentiation and Bone Development
Florian Otto,Anders P Thornell,Tessa Crompton,Angela Denzel,Kimberly C Gilmour,Ian R Rosewell,Gordon Stamp,Rosa S.P Beddington,Stefan Mundlos,Bjorn R. Olsen,Paul B. Selby,Michael John Owen +11 more
TL;DR: The Cbfa1 gene is essential for osteoblast differentiation and bone formation, and the C bfa1 heterozygous mouse is a paradigm for a human skeletal disorder.
Journal ArticleDOI
Coronary-Artery Calcification in Young Adults with End-Stage Renal Disease Who Are Undergoing Dialysis
William G. Goodman,Jonathan G. Goldin,Beatriz D. Kuizon,Chun Yoon,Barbara Gales,Donna Sider,Yan Wang,Joanie Chung,Aletha Emerick,Lloyd E. Greaser,Robert Elashoff,Isidro B. Salusky +11 more
TL;DR: Coronary-artery calcification is common and progressive in young adults with end-stage renal disease who are undergoing dialysis who are undergoing dialysis.
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Makoto Kuro-o,Matsumura Yutaka,H. Arawa,Hiroshi Kawaguchi,Tatsuo Suga,Toshihiro Utsugi,Yoshio Ohyama,Masahiko Kurabayashi,Tadashi Kaname,Eisuke Kume,H. Iwasaki,Akihiro Iida,Takako Shiraki-Iida,Satoshi Nishikawa,Ryozo Nagai,Yo-ichi Nabeshima,K. Sharma,L. Kelly,T. Dandekar +18 more
TL;DR: A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes in the mouse, including short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema as mentioned in this paper.