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

1)血管钙化是动脉粥样硬化的常见表现。探讨无机磷水平对人主动脉平滑肌细胞(HSMC)矿化的调节作用。在含有与高磷血症患者相似的磷酸盐水平的培养液中，HSMCs显示出矿物质沉积的剂量依赖性增加。机制研究表明，高磷处理的HSMCs增加了成骨细胞分化标志物的表达。高磷对HSMCs的影响是由钠依赖的磷酸共转运体(NPC)介导的，其特异性的NPC抑制剂磷酸甲酸抑制磷酸盐诱导的钙沉积的能力表明了这一点。经聚合酶链式反应和Northern印迹分析，证实HSMCs中的NPC为Pit-1。这些数据表明，升高的磷酸盐可能会刺激HSMC经历易于钙化的表型变化，并为表型…提供了新的解释2)孟克伯格内侧硬化症(MMS)是一种特征性的钙化动脉病变，表现为骨化生。我们用免疫组织化学方法研究了终末期肾病(ESRD)患者MMS中细胞凋亡和非胶原蛋白(NCP)如骨钙素(OC)和基质玻璃蛋白(MGP)在MMS发生中的作用。取自55例分析前患者的桡动脉标本。8例患者标本中检出MMS病变，其中6例为糖尿病引起的终末期肾病。原位末端标记法显示，只有病变处的平滑肌细胞(SMC)有凋亡细胞死亡。BAX在病变周围呈阳性表达。血管内皮生长因子主要在皮损周围的SMC中表达。在病变边界检测到OC和MGP。这些数据表明，中枢性SMC死亡可能有助于终末期肾病患者MMS的进展，而NCPs可能调节这一钙化过程。较少

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