Nikiforov Nikita G, Elizova Natalia V, Bukrinsky Michael, Dubrovsky Larisa, Makeev Vsevolod J, Wakabayashi Yoshiyuki, Liu Poching, Foxx Kathy K, Kruth Howard S, Jin Xueting, Zakiev Emile R, Orekhov Alexander N
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russian Federation.
GW School of Medicine and Health Sciences, George Washington University, 20037 Washington, DC, United States.
Curr Pharm Des. 2017;23(6):915-920. doi: 10.2174/1381612823666170125110128.
In this mini-review, the role of macrophage phenotypes in atherogenesis is considered. Recent studies on distribution of M1 and M2 macrophages in different types of atherosclerotic lesions indicate that macrophages exhibit a high degree of plasticity of phenotype in response to various conditions in microenvironment. The effect of the accumulation of cholesterol, a key event in atherogenesis, on the macrophage phenotype is also discussed. The article presents the results of transcriptome analysis of cholesterol-loaded macrophages revealing genes involved in immune response whose expression rate has changed the most. It turned out that the interaction of macrophages with modified LDL leads to higher expression levels of pro-inflammatory marker TNF-α and antiinflammatory marker CCL18. Phenotypic profile of macrophage activation could be a good target for testing of novel anti-atherogenic immunocorrectors. A number of anti-atherogenic drugs were tested as potential immunocorrectors using primary macrophage-based model.
在这篇小型综述中，探讨了巨噬细胞表型在动脉粥样硬化形成中的作用。近期关于M1和M2巨噬细胞在不同类型动脉粥样硬化病变中分布的研究表明，巨噬细胞在应对微环境中的各种条件时表现出高度的表型可塑性。还讨论了胆固醇积累（动脉粥样硬化形成中的关键事件）对巨噬细胞表型的影响。本文展示了对胆固醇负载巨噬细胞进行转录组分析的结果，揭示了免疫反应中表达率变化最大的相关基因。结果发现，巨噬细胞与修饰的低密度脂蛋白相互作用会导致促炎标志物肿瘤坏死因子-α和抗炎标志物CCL18的表达水平升高。巨噬细胞激活的表型特征可能是测试新型抗动脉粥样硬化免疫调节剂的良好靶点。使用基于原代巨噬细胞的模型对多种抗动脉粥样硬化药物作为潜在的免疫调节剂进行了测试。
