In the current study, we aimed to investigate the effects of miR-155 on CD4⁺ T cell-mediated immune response in the pathogenesis of atherosclerosis. CD34⁺ hematopoietic stem cells, CD4⁺ T lymphocytes, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) were harvested from the same donor. Knockdown of miR-155 in the CD4⁺ T cells was achieved by lentiviral transfection, whereas control RNA-transfected or untransfected lymphocytes were used as controls. The transfected CD4⁺ T cells were activated by incubating with oxidized low-density lipoprotein-treated dendritic cells. The proliferative capacities, phenotype distribution, and cytokine secretion profiles of the activated CD4⁺ T cells from different groups were evaluated. The activated lymphocytes were used to treat ECs co-cultivated with VSMCs. The ability of the CD4⁺ T cells to induce the apoptosis of the ECs and to promote the proliferation of the VSMCs was investigated. Inhibition of miR-155 was found to significantly reduce the proliferation rate of the transfected CD4⁺ T cells. CD4⁺ T lymphocytes transfected with the miR-155 inhibitor showed increased populations of T helper type 2 and regulatory T cells, as well as more production of anti-inflammatory cytokines. MiR-155 knockdown was also shown to significantly hamper the ability to CD4⁺ T cells to induce EC apoptosis and to promote the growth of VSMCs. Our data suggested that inhibition of miR-155 in CD4⁺ T cells could slow down the formation of atherosclerotic plaques. These results lay the groundwork for future research on the therapeutic potential of miR-155 against atherosclerosis-associated cardiovascular diseases.

中文翻译：

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在动脉粥样硬化的发病机理中，抑制microRNA-155对CD4 + T细胞介导的炎症反应具有抗炎作用。

在本研究中，我们旨在研究miR-155在动脉粥样硬化发病机理中对CD4 ⁺ T细胞介导的免疫反应的影响。CD34 ⁺造血干细胞，CD4 ⁺ T淋巴细胞，内皮细胞（ECs）和血管平滑肌细胞（VSMCs）均来自同一供体。通过慢病毒转染可实现CD4 ⁺ T细胞中miR-155的敲低，而将对照RNA转染或未转染的淋巴细胞用作对照。通过与经氧化的低密度脂蛋白处理的树突细胞孵育，激活转染的CD4 ⁺ T细胞。活化的CD4 ⁺的增殖能力，表型分布和细胞因子分泌谱评价了来自不同组的T细胞。活化的淋巴细胞用于治疗与VSMC共培养的EC。研究了CD4 ⁺ T细胞诱导ECs凋亡和促进VSMCs增殖的能力。发现抑制miR-155可显着降低转染的CD4 ⁺ T细胞的增殖速率。用miR-155抑制剂转染的CD4 ⁺ T淋巴细胞显示2型T辅助细胞和调节性T细胞的种群增加，并且抗炎细胞因子的产生更多。还显示了MiR-155敲低会显着阻碍CD4 ⁺的能力T细胞诱导EC凋亡并促进VSMC的生长。我们的数据表明，抑制CD4 ⁺ T细胞中的miR-155可以减缓动脉粥样硬化斑块的形成。这些结果为进一步研究miR-155对与动脉粥样硬化相关的心血管疾病的治疗潜力奠定了基础。