Department of Emergency Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Department of Emergency Medicine, The Fifth Hospital of Xi'an, Xi'an, Shaanxi 710082, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7205-7212. doi: 10.3892/mmr.2017.7524. Epub 2017 Sep 19.
Atherosclerosis is characterized by localized lesions distributed in the arterial tree due to the shear stress produced by blood flow. Endothelial cells are directly affected by alterations in blood flow. Dysfunction and injury to endothelial cells has been hypothesized to initiate the pathological processes of atherosclerosis. The present study aimed to investigate the mechanism of shear stress‑induced endothelial cellular apoptosis. Shear stress was generated using an artificial device to mimic the impact of disturbed blood flow on cultured human aortic endothelial cells (HAECs). Cellular apoptosis was assessed using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay; an ELISA assay was used to detect the produced interleukin (IL)‑1β; specific small interfering (si)RNA was used to knockdown the expression of interleukin‑1 receptor‑associated kinase 2 (IRAK2) in HAECs and the expression levels of 78 kDa glucose‑regulated protein, DNA damage‑inducible transcript 3 protein (CHOP), IRAK2 and IL‑1β were evaluated using western blotting. The results of the present study demonstrated that artificial shear stress induced endoplasmic reticulum (ER) stress, IL‑1β production and apoptosis in HAECs in a time‑dependent manner. The inhibition of ER stress, and treatment with interleukin‑1 receptor antagonist protein and siRNA against IRAK2 attenuated shear stress‑induced CHOP signaling‑mediated cellular apoptosis. Therefore, overproduction of IL‑1β exacerbated shear stress‑induced ER stress‑mediated apoptosis via the IRAK2/CHOP signaling pathway in endothelial cells.
动脉粥样硬化的特征是局部病变分布在动脉树中，这是由于血流产生的剪切力。内皮细胞直接受到血流变化的影响。内皮细胞功能障碍和损伤被假设为启动动脉粥样硬化的病理过程。本研究旨在探讨剪切力诱导内皮细胞凋亡的机制。使用人工装置产生剪切力，模拟对培养的人主动脉内皮细胞（HAEC）中紊乱血流的影响。使用末端脱氧核苷酸转移酶 dUTP 缺口末端标记法评估细胞凋亡；ELISA 法检测产生的白细胞介素（IL）-1β；特异性小干扰（si）RNA 敲低 HAEC 中白细胞介素 1 受体相关激酶 2（IRAK2）的表达，并使用 Western blot 法评估 78 kDa 葡萄糖调节蛋白、DNA 损伤诱导转录 3 蛋白（CHOP）、IRAK2 和 IL-1β 的表达水平。本研究结果表明，人工剪切力以时间依赖性方式诱导内皮细胞内质网（ER）应激、IL-1β 产生和凋亡。ER 应激的抑制以及白细胞介素 1 受体拮抗剂蛋白和针对 IRAK2 的 siRNA 的治疗减轻了剪切力诱导的 CHOP 信号通路介导的细胞凋亡。因此，IL-1β 的过度产生通过内皮细胞中的 IRAK2/CHOP 信号通路加剧了剪切力诱导的 ER 应激介导的凋亡。
