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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Ecklonia cava extracts decrease hypertension-related vascular calcification by modulating PGC-1α and SOD2.
TL;DR: In this article , Ecklonia cava extract (ECE) is known to increase peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) and SOD2.
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Development of a quantitative systems pharmacology model of chronic kidney disease: metabolic bone disorder
Adam E. Gaweda,Devin E. McBride,Eleanor D. Lederer,Eleanor D. Lederer,Michael E. Brier,Michael E. Brier +5 more
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Relationship of urine dopamine with phosphorus homeostasis in humans: the heart and soul study.
TL;DR: Higher dietary phosphorus absorption is associated with higher urineDA in humans, consistent with animal models, however, higher urine DA is not associated with FGF-23 or PTH, suggesting that known mechanisms of renal tubular handling of phosphorus may not be involved in the renal dopamine-phosphorus regulatory pathway in humans.
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The effect of sevelamer hydrochloride and calcium-based phosphate binders on mortality in hemodialysis patients: a need for more research.
TL;DR: The Renagel in New Dialysis (RIND) extension study and the Dialysis Clinical Outcomes Revisted (DCOR) study were the first clinical trials to compare the effects of calcium-based phosphate binders and sevelamer hydrochloride on mortality in hemodialysis patients.
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Impact of Serum Phosphorus Levels on Outcomes After Implantation of Drug-Eluting Stents in Patients on Hemodialysis.
Tatsuyuki Sato,Jiro Aoki,Ken Kozuma,Yasuyuki Maruyama,Kenya Nasu,Masaya Otsuka,Kenji Ando,Kiyoshi Hibi,Yoshiki Uehara,Kengo Tanabe,Yuji Ikari +10 more
TL;DR: Lowering of serum phosphorus levels beyond the current recommended range may be considered in HD patients who undergo DES implantation, following a post-hoc study of the OUCH study series.
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.