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.
journal_name
Circ Resjournal_title
Circulation researchauthors
Jono S,McKee MD,Murry CE,Shioi A,Nishizawa Y,Mori K,Morii H,Giachelli CMdoi
10.1161/01.res.87.7.e10subject
Has Abstractpub_date
2000-09-29 00:00:00pages
E10-7issue
7eissn
0009-7330issn
1524-4571journal_volume
87pub_type
杂志文章abstract::Autoregulatory responses to alterations in arterial or venous perfusion pressure were determined for individual arterioles within the rat cremaster muscle. The cremaster muscle of pentobarbital anesthetized rats (50 mg/kg, ip) was surgically exposed and maintained in a controlled tissue bath for visualization by in vi...
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