Phosphate Regulation of Vascular Smooth Muscle Cell Calcification : Significance of phosphate transporter in atherosclerotic lesion.
| Project/Area Number |
12671122
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Osaka City University |
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Principal Investigator |
OKUNO Yasuhisa Department of Cardiovascular Medicine Associate Prefessor institute of Geriatrics and Medical Science, osaka city university, 大学院・医学研究科, 助教授 (80152429)
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| Co-Investigator(Kenkyū-buntansha) |
JONO Shuichi Department of Metabolism, Endocrinology Research Associate and Molecular Medicine, osaka city university, 大学院・医学研究科, 助手 (60336790)
SHIOI Atsushi Department of Cardiovascular Medicine Lecturer institute of Geriatrics and Medical Science, osaka city university Lecturer, 大学院・医学研究科, 講師 (90260801)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | vascular calcification / inorganic phosphate / phosphate cotransporter / smooth muscle cell / apoptosis / Monckeberg's calcification / chronic renal failure / VEGF / 血管平滑筋細胞 / 骨基質蛋白 / Klothok / oマウス |
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| Research Abstract |
1) Vascular calcification is a common finding in atherosclerosis. The ability of inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralization was examined. HSMCs in media containing phosphate levels comparable to those seen in hyperphosphatemic individuals showed dose-dependent increases in mineral deposition. Mechanistic studies revealed that elevated phosphate treatment of HSMCs enhanced the expression of the osteoblastic differentiation markers. The effect 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 dependency inhibit phosphate-induced calcium deposition. The NPC in HSMCs was identified as Pit-1 with PCR and Northern blot analyses. These data suggest that elevated phosphate may stimulate HSMCs to undergo phenotypic changes that predispose to calcification and that offer a novel explanation of the phenom
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enon of vascular calcification under hyperphosphatemic conditions.
2) Monckeberg's medial sclerosis (MMS) is one of the characteristic calcified arterial lesions and exhibits osseous metaplasia. We investigated immunohistochemistry the roles of apoptotic cell death and non-colagenous proteins (NCPs) such as osteocalcin(OC) and matrix gla protein (MGP) in the development of MMS in patients with end-stage renal disease (ESRD). Radial artery specimens were obtained from 55 preanalysis patients. MMS lesions were detected in the specimens derived from 8 patients of whom 6 had diabetes mellitus as the cause of ESRD. Only in the lesions, apoptotic cell death demonstrated by TUNEL method was detected in smooth muscle cells (SMCs). Bax was demonstrated around the lesions. VEGF was expressed mainly in SMCs around the lesions. OC and MGP were detected at the boundaries of the lesions.These data suggest that medial SMC death may contribute to progression of MMS in patients with ESRD and that NCPs may modulate this calcifying process. Less
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Report
(3 results)
Research Products
(14 results)
