Oscillating shear stress mediates mesenchymal transdifferentiation of EPCs by the Kir2.1 channel
Oscillating shear stress mediates mesenchymal transdifferentiation of EPCs by the Kir2.1 channel
复制标题
振荡剪切应力通过 Kir2.1 通道介导 EPC 的间质转分化
DOI：
10.1007/s00380-020-01625-w
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发表时间：
2020-05-24
影响因子：
1.5
通讯作者：
Cheng，Min
中科院分区：
文献类型：
--
作者：
Li，Jifeng;He，Yanting;Cheng，Min
尽管内皮祖细胞（endothelial progenitor cells，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其在内皮损伤的修复中发挥着双刃剑的作用。本研究旨在探讨Kir2.1离子通道在振荡切应力（oscillating shear stress，OSS）作用下对内皮祖细胞（endothelial progenitor cells，EPCs）转分化的影响，以及病理性血管重构的分子机制。用平行流室系统模拟的OSS（± 3.5达因/cm 2，1 Hz）处理EPCs。结果表明，OSS促进EPCs表达间充质细胞标志物α-SMA和SM 22。另外，OSS还可增加EPCs Kir2.1的表达。Kir2.1的下调降低了OSS诱导的EPC间充质转分化。Kir2.1的过表达可抑制EPCs的血管生成能力。同时，在大鼠颈动脉球囊损伤模型中，内皮祖细胞上Kir2.1的过表达使颈动脉图尼卡内膜增厚。综上所述，这些数据表明，OSS可以通过增加Kir2.1的表达来促进EPCs的转分化。这项研究为深入了解心血管疾病的发病机制提供了新的视角，并为Kir2.1作为潜在的治疗靶点提供了证据。
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/cm2, 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.