Li Jifeng, He Yanting, Bu Hongnan, Wang Meiyue, Yu Jie, Li Lanlan, Li Hong, Zhang Xiaoyun, Cui Xiaodong, Cheng Min
School of Basic Medical Sciences, Weifang Medical University, Weifang, 261053, Shandong, People's Republic of China.
Department of Gynaecology and Obstetrics, The 89 Hospital of Chinese PLA, Weifang, 261021, Shandong, People's Republic of China.
Heart Vessels. 2020 Oct;35(10):1473-1482. doi: 10.1007/s00380-020-01625-w. Epub 2020 May 24.
Although endothelial progenitor cells (EPCs) are considered to be an essential source of vascular endothelial repair, their bidirectional differentiation determines that they play a double-edged role in the restoration of endothelial injury. In this research, we investigated the effect of Kir2.1 ion channel on the transdifferentiation of endothelial progenitor cells (EPCs) under the oscillating shear stress (OSS) and the molecular mechanisms underlying the pathological vascular remodeling. EPCs were treated with OSS (± 3.5 dynes/cm, 1 Hz) simulated with the parallel flow chamber system. The results have shown that OSS promoted the expression of α-SMA and SM22, markers of mesenchymal cells on EPCs. Moreover, OSS also increased expression of Kir2.1 in EPCs. The down-regulation of Kir2.1 reduced OSS-induced EPC mesenchymal transdifferentiation. The overexpression of Kir2.1 suppressed the angiogenic abilities of EPCs in vitro. In parallel, the overexpression of Kir2.1 on EPCs thickened the carotid tunica intima in rat carotid artery balloon injured model in vivo. Taken together, those data indicated that the OSS could facilitate the transdifferentiation of EPCs by increasing Kir2.1 expression. This study provides a novel insight into the pathogenesis of cardiovascular diseases and gives evidence for Kir2.1 as a potential therapeutic target.
尽管内皮祖细胞（EPCs）被认为是血管内皮修复的重要来源，但其双向分化决定了它们在血管内皮损伤修复中发挥着双刃剑的作用。在本研究中，我们研究了Kir2.1离子通道在振荡剪切力（OSS）作用下对内皮祖细胞（EPCs）转分化的影响以及病理性血管重塑的分子机制。使用平行流室系统模拟的OSS（±3.5达因/平方厘米，1赫兹）处理EPCs。结果表明，OSS促进了EPCs上间充质细胞标志物α-SMA和SM22的表达。此外，OSS还增加了EPCs中Kir2.1的表达。Kir2.1的下调减少了OSS诱导的EPC间充质转分化。Kir2.1的过表达抑制了EPCs在体外的血管生成能力。同时，在体内大鼠颈动脉球囊损伤模型中，EPCs上Kir2.1的过表达使颈动脉内膜增厚。综上所述，这些数据表明OSS可通过增加Kir2.1的表达促进EPCs的转分化。本研究为心血管疾病的发病机制提供了新的见解，并为Kir2.1作为潜在治疗靶点提供了证据。
