2020 年第 3 期 第 15 卷

高磷诱导动脉中层钙化相关信号通路的研究进展

Signal pathways involving in arterial medial calcification induced by high phosphate

作者：黄晓雯何伟春

英文作者：

单位：南京医科大学第二附属医院肾内科210003 

英文单位：

关键词：动脉中层钙化；高磷；信号通路；血管平滑肌细胞

英文关键词：

• 摘要：

• 【摘要】动脉中层钙化（AMC）是慢性肾脏病（CKD）患者常见的血管钙化类型。不同于动脉粥样斑块部位的内膜钙化，AMC是羟基磷灰石钙在动脉中层沉积所致。常见于CKD患者的高磷血症可诱导AMC的形成，位于动脉中层的血管平滑肌细胞（VSMCs）在AMC的形成中发挥重要作用。高磷环境下VSMCs向成骨细胞分化产生并释放作为钙化晶核形成位点的含钙磷的基质囊泡，促进钙化的发生。这一AMC形成过程中的关键步骤受VSMCs内多条信号通路调控，包括Wnt/β-连环蛋白信号通路、核因子κB信号通路、腺苷酸活化蛋白激酶-生长抑制特异性基因6/Axl-磷脂酰肌醇3-激酶/蛋白激酶B-Bcl2信号通路、转化生长因子β/Smad信号通路等。

  
  

• 【Abstract】Arterial medial calcification(AMC) is a prevalent type of vascular calcification in patients with chronic kidney disease(CKD). Unlike the intimal calcification in atherosclerotic plaque, AMC is characterized by the deposition of calcium hydroxyapatite in arterial media, which contributes to the hardening of vessels. Hyperphosphatemia is a common clinical feature in patients with CKD and a potent inducer of AMC. In a high phosphorous environment, vascular smooth muscle cells(VSMCs) located in the medial layer of arterial wall undergo a process of VSMCs to osteogenic transdifferentiation(VOT), leading to the production and release of matrix vesicles containing calcium and phosphate, where are the sites of calcified nanocrystal development. VOT is the most critical step during the formation of AMC. Several cellular signal cascades are involved in the pathogenesis of VOT induced by high phosphate, including Wnt/β-catenin signal pathway, nuclear factor-kB signal pathway, adenine monophosphate activated protein kinase-growth arrest specific gene-6/Axl-phosphatidylinositol-3-kinase/protein kinase B-Bcl2 signal pathway, transforming growth factor-β/Smad signal pathway and so on.