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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Chronic kidney disease and vascular remodelling: molecular mechanisms and clinical implications.
Marie Briet,Kevin D. Burns +1 more
TL;DR: The present review details the mechanisms involved in arterial calcification and arterial remodelling associated with CKD, and provides the clinical consequences of large and small artery stiffness and remodelling in CKD patients.
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Inhibitors of calcification in blood and urine.
TL;DR: A review of calcification inhibitors can be found in this paper, which summarizes current experimental and clinical data underlining the biological importance of these calcification inhibitor and suggests that dys-regulations of such calcification inhibition may contribute to progressive calcification.
Journal ArticleDOI
Serum phosphate as a risk factor for cardiovascular events in people with and without chronic kidney disease: a large community based cohort study.
Andrew McGovern,Simon de Lusignan,Simon de Lusignan,Jeremy van Vlymen,Harshana Liyanage,Charles Richard Tomson,Hugh Gallagher,Hugh Gallagher,Meena Rafiq,Simon Jones +9 more
TL;DR: Serum phosphate is associated with cardiovascular events in people with and without CKD and further research is required to determine the mechanisms underlying these associations.
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Calcium phosphate metabolism and cardiovascular disease in patients with chronic kidney disease.
TL;DR: Evidence is presented describing the impact of calcification‐induced arterial stiffness on cardiovascular outcomes of patients with ESRD, along with data relating altered mineral metabolism to all‐cause and cardiovascular mortality.
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Unified theory on the pathogenesis of Randall’s plaques and plugs
TL;DR: Should this theory hold true, developing an understanding of the cellular mechanisms involved in progression of a small, basic interstitial plaque to that of an expanding, penetrating plaque could assist in the development of new therapies for stone prevention.
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing
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