Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Japan.
Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Japan; Department of Perinatal and Neonatal Medicine, Aichi Medical University, Nagakute, Japan.
Exp Cell Res. 2020 Aug 15;393(2):112094. doi: 10.1016/j.yexcr.2020.112094. Epub 2020 May 18.
Atherosclerosis is an important underlying cause of cardiovascular diseases; vascular endothelial cells play a vital role in inflammatory responses in the initial steps of atherosclerosis. High levels of the pro-inflammatory cytokine interleukin-6 (IL-6) long have been considered a risk factor in the development and complications of atherosclerotic disease. However, it is still controversial whether IL-6 is atherogenic or atheroprotective. Recently, miR-126-3p, an endothelial cell-specific microRNA, has been proposed as an atheroprotective molecule. Therefore, we investigated whether IL-6 accelerates endothelial cell responses through the suppression of miR-126-3p expression in human endothelial cell line EA.hy926. IL-6 yielded concentration-dependent decreases in miRNA-126-3p accumulation in EA.hy926 cells, leading in turn to increased expression of genes targeted by miRNA-126-3p. In addition, adhesion of the human monocyte cell line THP-1 was enhanced by the exposure of EA.hy926 cells to IL-6, with associated increases in the levels of the adhesion molecule intercellular adhesion molecule-1 (ICAM-1). Suppression of miR-126-3p expression resulted in upregulation of miRNA-126-3p-regulated genes, enhanced adhesion of THP-1 cells, and increased ICAM-1 accumulation in EA.hy926 cells. In contrast, miR-126-3p overproduction had the opposite effects. The regulation of miRNA-126-3p by IL-6 may have important implications for the development of novel protective therapies targeting atherosclerosis.
动脉粥样硬化是心血管疾病的重要潜在原因；血管内皮细胞在动脉粥样硬化的初始步骤中的炎症反应中起着至关重要的作用。高水平的促炎细胞因子白细胞介素 6 (IL-6) 长期以来一直被认为是动脉粥样硬化疾病发展和并发症的危险因素。然而，IL-6 是否具有动脉粥样硬化作用或具有动脉保护作用仍存在争议。最近，miR-126-3p，一种内皮细胞特异性 microRNA，被认为是一种具有动脉保护作用的分子。因此，我们研究了 IL-6 是否通过抑制人内皮细胞系 EA.hy926 中的 miR-126-3p 表达来加速内皮细胞反应。IL-6 在 EA.hy926 细胞中产生浓度依赖性的 miR-126-3p 积累减少，从而导致 miR-126-3p 靶向基因的表达增加。此外，EA.hy926 细胞暴露于 IL-6 会增强人单核细胞系 THP-1 的黏附，同时黏附分子细胞间黏附分子-1 (ICAM-1) 的水平也会增加。抑制 miR-126-3p 表达导致 miR-126-3p 调控基因的上调、THP-1 细胞的黏附增强以及 EA.hy926 细胞中 ICAM-1 积累增加。相反，miR-126-3p 的过表达则产生相反的效果。IL-6 对 miR-126-3p 的调节可能对靶向动脉粥样硬化的新型保护治疗具有重要意义。
