Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
Department of Perinatal and Neonatal Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute 480-1195, Japan.
Int J Mol Sci. 2023 Feb 1;24(3):2829. doi: 10.3390/ijms24032829.
Atherosclerosis can lead to cardiovascular and cerebrovascular diseases. Atherosclerotic plaque formation is promoted by the accumulation of inflammatory cells. Therefore, modulating monocyte recruitment represents a potential therapeutic strategy. In an inflammatory state, the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) is upregulated in endothelial cells. We previously reported that miR-1914-5p in endothelial cells suppresses interleukin (IL)-1β-induced ICAM-1 expression and monocyte adhesion to endothelial cells. However, whether monocyte miR-1914-5p affects monocyte recruitment is unclear. In this study, IL-1β decreased miR-1914-5p expression in a human monocyte cell line. Moreover, miR-1914-5p inhibition enhanced adhesion to endothelial cells with the upregulation of macrophage-1 antigen (Mac-1), a counter-ligand to ICAM-1. Transmigration through the endothelial layer was also promoted with the upregulation of monocyte chemotactic protein-1 (MCP-1). Furthermore, a miR-1914-5p mimic suppressed IL-1β-induced monocyte adhesion and transmigration in monocytes with Mac-1 and MCP-1 downregulation. Further investigation of miR-1914-5p in monocytes could lead to the development of novel diagnostic markers and therapeutic strategies for atherosclerosis.
动脉粥样硬化可导致心血管和脑血管疾病。炎症细胞的积累促进了动脉粥样硬化斑块的形成。因此,调节单核细胞募集代表了一种潜在的治疗策略。在炎症状态下,内皮细胞中细胞间黏附分子-1(ICAM-1)等黏附分子的表达上调。我们之前的研究表明,内皮细胞中的 miR-1914-5p 抑制白细胞介素(IL)-1β诱导的 ICAM-1 表达和单核细胞与内皮细胞的黏附。然而,单核细胞 miR-1914-5p 是否影响单核细胞募集尚不清楚。在这项研究中,IL-1β降低了人单核细胞系中 miR-1914-5p 的表达。此外,miR-1914-5p 的抑制作用增强了与巨噬细胞-1 抗原(Mac-1)的黏附,Mac-1 是 ICAM-1 的反配体。通过内皮层的迁移也通过单核细胞趋化蛋白-1(MCP-1)的上调而促进。此外,miR-1914-5p 模拟物抑制了 Mac-1 和 MCP-1 下调的单核细胞中 IL-1β诱导的单核细胞黏附和迁移。进一步研究单核细胞中的 miR-1914-5p 可能为动脉粥样硬化的新诊断标志物和治疗策略的发展提供依据。