Zhang Kai, Kong Jing, Liu Bin, Meng Xiao
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, 250012, Shandong, China.
Heart Vessels. 2020 Feb;35(2):278-283. doi: 10.1007/s00380-019-01491-1. Epub 2019 Sep 9.
COX-2 contributes to local inflammation in atherosclerotic lesions. Regulatory T cells (Tregs) enhance the stability of atherosclerotic plaques. The aim of this study was to detect the potential relationship between Tregs and COX-2 in vulnerable plaques. Thirty ApoE mice were fed a high-fat diet, and a silastic perivascular collar was placed around the right common carotid artery to induce vulnerable plaques. Eight weeks after collar placement, the mice were divided randomly into three groups: control, PBS, and Treg groups. Four weeks later, the right common carotid arteries were collected to detect the expression of COX-2. The results showed that Tregs significantly suppressed the expression of COX-2 in vulnerable plaques. In an in vitro experiment, RAW264.7 cells were divided randomly into three groups, which were precultured without T cells or with CD4 + CD25- T cells or Tregs for 48 h with an anti-CD3 antibody; then the cells were stimulated with LPS for 24 h. The RAW264.7 cells were harvested for RT-PCR and western blot assays and the results showed that Tregs downregulated COX-2 expression in RAW264.7 cells. Therefore, Tregs inhibited the expression of COX-2 in vulnerable plaques and macrophages, and COX-2 inhibition may be an important effect of Tregs that results in atherosclerotic plaque stabilization.
环氧化酶-2(COX-2)促进动脉粥样硬化病变中的局部炎症。调节性T细胞(Tregs)增强动脉粥样硬化斑块的稳定性。本研究的目的是检测Tregs与易损斑块中COX-2之间的潜在关系。给30只载脂蛋白E基因敲除小鼠喂食高脂饮食,并在右侧颈总动脉周围放置硅橡胶血管外膜套环以诱导易损斑块形成。套环放置8周后,将小鼠随机分为三组:对照组、磷酸盐缓冲液(PBS)组和Treg组。4周后,收集右侧颈总动脉以检测COX-2的表达。结果显示,Tregs显著抑制易损斑块中COX-2的表达。在体外实验中,将RAW264.7细胞随机分为三组,分别在无T细胞、有CD4+CD25-T细胞或Tregs的情况下,用抗CD3抗体预培养48小时;然后用脂多糖(LPS)刺激细胞24小时。收集RAW264.7细胞进行逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析,结果显示Tregs下调RAW264.7细胞中COX-2的表达。因此,Tregs抑制易损斑块和巨噬细胞中COX-2的表达,COX-2抑制可能是Tregs导致动脉粥样硬化斑块稳定的重要作用。