Vascular calcification: In vitro evidence for the role of inorganic phosphate
Vascular calcification: In vitro evidence for the role of inorganic phosphate
复制标题
DOI：
10.1097/01.asn.0000081663.52165.66
复制
发表时间：
2003-09-01
影响因子：
13.6
通讯作者：
Giachelli, CM
中科院分区：
文献类型：
--
作者：
Giachelli, CM
尿毒症患者容易发生广泛的异位骨外钙化，这是由全身无机磷酸盐（Pi）失衡引起的。这一过程可能会产生严重的后果，特别是当它导致血管钙化时。最近的一项研究检查了培养的人主动脉平滑肌细胞对不同水平的细胞外Pi的反应。暴露于与尿毒症患者相似的Pi水平（> 1.4 mmol/L）的细胞培养钙沉积呈剂量依赖性增加。本研究的结果还确定了磷酸盐升高在将这些细胞的血管表型转化为成骨表型中的作用，从而产生了钙化的倾向。pi诱导的变化包括成骨标志物骨钙素和核心结合因子-1基因的表达增加，后者被认为是成骨细胞分化的关键“主基因”。这些变化在暴露于高磷酸盐水平后早期发生，似乎是由钠依赖性磷酸盐共转运蛋白Pit-1 （Glvr-1）介导的。血管细胞的钙化似乎也发生在没有矿物质失衡的情况下，但在血小板衍生生长因子（一种有效的致动脉粥样硬化因子）存在的情况下。综上所述，这些数据表明，血管细胞的钙化可以在富含磷酸盐的环境中早期发生，类似于肾功能衰竭患者的情况，以及在正常磷条件下富含血小板衍生生长因子的动脉粥样硬化区。从临床角度来看，早期控制或预防高磷血症似乎可以降低透析患者的冠状动脉钙化及其相关的发病率和死亡率。
Uremic patients are prone to widespread ectopic extraskeletal calcification resulting from an imbalance of systemic inorganic phosphate (Pi). There can be serious consequences of this process, particularly when it results in the calcification of the vasculature. A recent study examined the response of cultured human aortic smooth muscle cells to varying levels of extracellular Pi. Cells that were exposed to Pi levels similar to those seen in uremic patients (> 1.4 mmol/L) showed dose-dependent increases in cell culture calcium deposition. The results of this study also defined the role of elevated phosphate in transforming the vascular phenotype of these cells to an osteogenic phenotype, such that a predisposition for calcification was created. Pi-induced changes included increased expression of the osteogenic markers osteocalcin and core-binding factor-1 genes, the latter of which is considered a "master gene" critical for osteoblast differentiation. These changes occur early after exposure to high phosphate levels and seem to be mediated by a sodium-dependent phosphate co-transporter, Pit-1 (Glvr-1). Calcification of vascular cells also seems to occur in the absence of a mineral imbalance but in the presence of platelet-derived growth factor, a potent atherogenic factor. Taken together, these data suggest that calcification of vascular cells can occur early in a phosphate-rich environment similar to that seen in patients with renal failure and in a platelet-derived growth factor-rich atherosclerotic region under normal phosphorus conditions. From a clinical viewpoint, it seems that early control or prevention of hyperphosphatemia may reduce coronary calcification and its associated morbidity and mortality for patients on dialysis.