Department of Cardiology, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Immunol Cell Biol. 2010 Jul;88(5):555-64. doi: 10.1038/icb.2010.16. Epub 2010 Mar 2.
The upregulation of Th1 cells has been suggested to have an essential function in the development of atherosclerosis (AS). Recent studies indicate that miR-146a is a microRNA specifically and highly expressed in Th1-driven autoimmune disease. The aim of the study was to investigate the possible mechanisms of the miR-146a in the onset of acute coronary syndrome (ACS). The results showed that the expression of miR-146a in peripheral blood mononuclear cells (PBMCs) was significantly increased in patients with ACS. We showed that overexpression of miR-146a in PBMCs could significantly upregulate the function of Th1 cells. Furthermore, we showed that miR-146a treatment could modulate the Th1 differentiation through posttranscriptional enhancing the T-bet pathway in PBMCs. In addition, this study also provided evidence that miR-146a treatment in vitro could induce the protein expression of TNF-alpha, MCP-1, NF-kappaB p65, which are key pro-inflammatory cytokines and critical transcription factor in AS. In contrast, miR-146a inhibitor could attenuate these phenomena significantly. The results support the concept that miR-146a may be a novel regulatory factor in Th1 differentiation and a new therapeutic target for AS and ACS.
Th1 细胞的上调被认为在动脉粥样硬化（AS）的发展中具有重要作用。最近的研究表明，miR-146a 是一种在 Th1 驱动的自身免疫性疾病中特异性和高度表达的 microRNA。本研究旨在探讨 miR-146a 在急性冠脉综合征（ACS）发病机制中的可能机制。结果表明，ACS 患者外周血单个核细胞（PBMC）中 miR-146a 的表达显著增加。我们表明，在 PBMC 中转染 miR-146a 可显著上调 Th1 细胞的功能。此外，我们表明，miR-146a 治疗可通过在 PBMC 中转录后增强 T-bet 途径来调节 Th1 分化。此外，本研究还提供了证据表明，miR-146a 体外处理可诱导 TNF-α、MCP-1、NF-kappaB p65 的蛋白表达，这些是 AS 中的关键促炎细胞因子和关键转录因子。相比之下，miR-146a 抑制剂可显著减弱这些现象。研究结果支持 miR-146a 可能是 Th1 分化的新调节因子和 AS 和 ACS 的新治疗靶点的概念。
