Phosphate Regulation of Vascular Smooth Muscle Cell Calcification : Significance of phosphate transporter in atherosclerotic lesion.

血管平滑肌细胞钙化的磷酸盐调节：磷酸盐转运蛋白在动脉粥样硬化病变中的意义。

• 批准号: 12671122
• 负责人: OKUNO Yasuhisa
• 金额: $ 1.73万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671122/
• 关键词: 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

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 … More 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

1)血管钙化是动脉粥样硬化的常见表现。研究了无机磷酸盐水平调节人主动脉平滑肌细胞（HSMC）培养矿化的能力。培养基中含有磷酸盐水平的HSMC与高磷酸盐血症个体中观察到的水平相当，显示矿物质沉积呈剂量依赖性增加。机制研究表明，高磷酸盐处理的HSMCs的成骨细胞分化标志物的表达增强。磷酸盐升高对HSMCs的影响是由钠依赖性磷酸盐协同转运蛋白（NPC）介导的，如特定NPC抑制剂膦甲酸剂量依赖性抑制磷酸盐诱导的钙沉积的能力所示。经PCR和北方杂交鉴定，HSMCs中的NPC为Pit-1。这些数据表明，磷酸盐升高可能刺激HSMCs发生表型变化，使其易于钙化，并为HSMCs的钙化现象提供了新的解释。 ...更多信息 Monckeberg's medial sclerosis（MMS）是一种典型的钙化性动脉病变，表现为骨化生。我们研究了终末期肾病（ESRD）患者中细胞凋亡和非胶原蛋白（NCPs）如骨钙素（OC）和基质糖蛋白（MGP）在MMS发生中的作用。桡动脉标本来自55例分析前患者。MMS病变检测来自8例患者的标本，其中6例糖尿病作为ESRD的原因。TUNEL法检测到平滑肌细胞凋亡。Bax在病变周围表达。VEGF主要表达于病变周围的平滑肌细胞。OC和MGP在病变的边界处被检测到。这些数据表明，中膜SMC死亡可能有助于ESRD患者MMS的进展，NCP可能调节这一钙化过程。少

项目成果

Okuno Y.: "Moncheberg's calcification in diabetes mellitus"COMPLICATION.. 6 (2). 200-208 (2001)

Okuno Y.：“糖尿病中的 Moncheberg 钙化”并发症.. 6 (2)。

Jono S., et al.: "Phosphate regulation of vascular smooth muscle cell calcification"Circ. Res.. 87. e10-e17 (2000)

Jono S. 等人：“血管平滑肌细胞钙化的磷酸盐调节”Circ。

Giachelli C. M. et al.: "Vascular calcification and inorganic phosphate"Am. J. Kidney Dis.. 38 (Supple 1). 34-37 (2001)

Giachelli C. M. 等人：“血管钙化和无机磷酸盐”Am。

Shioi A,Jono S,Okuno Y et al: "Mechanism of Atherosclerotic Calcification"Zeitsscrift fur Kardiologie. 89 suppl2. 75-89 (2000)

Shioi A、Jono S、Okuno Y 等人：“动脉粥样硬化钙化的机制”Zeitsscrift Fur Kardiologie。

Shioi A. et al.: "Monckeberg's medial sclerosis and inorganic phosphate in uremia"Am. J. Kidney Dis.. 38(Suppl1). 47-49 (2001)

Shioi A. 等人：“蒙克伯格内侧硬化症和尿毒症中的无机磷酸盐”Am。