Rudolf-Virchow-Center/DFG Research Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider Str. 2, Haus D15, 97080 Würzburg, Germany.
Thromb Haemost. 2012 Apr;107(4):626-33. doi: 10.1160/TH11-08-0603. Epub 2012 Feb 8.
Regarded as a chronic inflammatory disease of the vessel wall, the development of atherosclerotic lesions is shaped by immune responses and their regulation. Macrophages and dendritic cells are positioned at the crossroad of innate and adaptive immune responses by sensing atherogenic danger signals and by taking up and presenting antigens. T helper cells and auto-antibodies produced by B cells, together with their cytokine responses in turn modulate atheroprogression. In addition, platelets contribute to atherosclerosis by multiple pathways. microRNAs (miRNAs) that post-transcriptionally regulate gene expression may thus critically control immune cell differentiation and functions during plaque evolution. This review summarises the role of miRNAs in regulating lipid uptake and expression of inflammatory mediators in monocytes/macrophages and dendritic cells, in lymphocyte functions with a focus on T helper cell responses, as well as in platelet biology, and the implications of altering these functions in vascular pathology and atherosclerosis. T systematically survey miRNA functions in controlling molecular mechanisms and immune responses in atherosclerosis holds potential for the development of novel miRNA-based strategies for therapies targeting inflammation and immunity in atherosclerosis.
被认为是血管壁的一种慢性炎症性疾病,动脉粥样硬化病变的发展受免疫反应及其调节的影响。巨噬细胞和树突状细胞通过感应动脉粥样硬化危险信号以及摄取和呈递抗原,处于先天和适应性免疫反应的交汇点。T 辅助细胞和 B 细胞产生的自身抗体以及它们的细胞因子反应反过来调节动脉粥样硬化的进展。此外,血小板通过多种途径促进动脉粥样硬化的形成。微小 RNA(miRNA)可以通过转录后调控基因表达,从而在斑块演变过程中对免疫细胞的分化和功能进行关键控制。这篇综述总结了 miRNA 在调节单核细胞/巨噬细胞和树突状细胞中脂质摄取和炎症介质表达、淋巴细胞功能(重点是 T 辅助细胞反应)以及血小板生物学中的作用,以及改变这些功能在血管病理学和动脉粥样硬化中的意义。系统地研究 miRNA 在控制动脉粥样硬化中分子机制和免疫反应的功能,为开发基于 miRNA 的新型治疗策略以靶向动脉粥样硬化中的炎症和免疫反应提供了可能。