Department of Cardiology, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing, China.
Eur Rev Med Pharmacol Sci. 2017 Jun;21(11):2725-2733.
Mounting evidence suggests the role of microRNAs (miRNAs) in regulating inflammatory responses in various vascular diseases. Inflammation is the key mechanism leading to atherosclerosis (AS) and various miRNAs are aberrantly expressed in response to AS pathophysiology. However, there are very limited studies that serve to elucidate the role of specific miRNA in in vivo or in vitro AS models.
Microarray analysis of blood plasma of apolipoprotein deficient (apoE-/-) mice was performed followed by the confirmation using qPCR. Bone marrow mononuclear cells (BMMCs), plasma, and vessel tissue were obtained from apoE-/- mice that were induced with miR-126 mimic or inhibitor. Ox-LDL-induced THP-1 macrophages served as in vitro AS model. The release of inflammatory cytokines was detected using ELISA. The regulatory effect of miR-126 on MAP3K10 was confirmed by luciferase reporter activity and immunohistochemical analyses.
The results showed that the miR-126 exhibited a greater fold change of expression in AS mice. Further, the functional role of miR-126 in atherosclerosis pathophysiology was demonstrated both in vivo and in vitro. miR-126 reduced the cytokine release and also decreased the AS progression. miR-126 was also found to be involved in mitogen-associated protein kinase (MAPK) signaling pathway. MAP3K10 was identified to be a direct target.
miR-126 might serve as a biomarker of AS and its over-expression might prevent the AS progression and development.
越来越多的证据表明 microRNAs（miRNAs）在调节各种血管疾病中的炎症反应中发挥作用。炎症是导致动脉粥样硬化（AS）的关键机制，各种 miRNA 在外周动脉疾病的病理生理学过程中表达异常。然而，只有非常有限的研究阐明了特定 miRNA 在体内或体外 AS 模型中的作用。
对载脂蛋白缺陷（apoE-/-）小鼠的血浆进行微阵列分析，然后使用 qPCR 进行验证。从接受 miR-126 模拟物或抑制剂诱导的 apoE-/-小鼠中获得骨髓单核细胞（BMMCs）、血浆和血管组织。用 ox-LDL 诱导 THP-1 巨噬细胞作为体外 AS 模型。使用 ELISA 检测炎症细胞因子的释放。通过荧光素酶报告活性和免疫组织化学分析证实了 miR-126 对 MAP3K10 的调节作用。
结果表明，miR-126 在 AS 小鼠中的表达变化幅度更大。此外，miR-126 在体内和体外均证明了其在动脉粥样硬化发病机制中的功能作用。miR-126 减少了细胞因子的释放，也减少了 AS 的进展。miR-126 还参与丝裂原激活蛋白激酶（MAPK）信号通路。鉴定出 MAP3K10 是其直接靶标。
miR-126 可能作为 AS 的生物标志物，其过表达可能阻止 AS 的进展和发展。
