Department of Internal Medicine and Radboud Center for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands (D.F.-G., S.B., M.G.N., N.P.R.).
Department of Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, Germany (M.G.N.).
Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):62-69. doi: 10.1161/ATVBAHA.120.314216. Epub 2020 Nov 5.
Atherosclerosis is characterized by incessant inflammation in the arterial wall in which monocytes and macrophages play a crucial role. During the past few years, it has been reported that cells from the innate immune system can develop a long-lasting proinflammatory phenotype after brief stimulation not only with microbial products but also endogenous atherogenic stimuli. This persistent hyperactivation of the innate immune system is termed trained immunity and can contribute to the pathophysiology of atherosclerosis. Trained immunity is mediated via epigenetic and metabolic reprogramming and occurs both in mature innate immune cells as well as their bone marrow progenitors. In addition to monocytes, other innate immune and nonimmune cells involved in different stages of atherosclerosis can develop comparable memory characteristics. This mechanism provides exciting novel pharmacological targets that can be used to prevent or treat cardiovascular diseases.
动脉粥样硬化的特征是动脉壁内持续不断的炎症,其中单核细胞和巨噬细胞起着至关重要的作用。在过去的几年中,据报道,先天免疫系统的细胞在受到微生物产物和内源性动脉粥样硬化刺激物的短暂刺激后,不仅可以发展出持久的促炎表型。这种先天免疫系统的持续过度激活被称为训练有素的免疫,可能导致动脉粥样硬化的病理生理学改变。训练有素的免疫是通过表观遗传和代谢重编程介导的,发生在成熟的先天免疫细胞及其骨髓祖细胞中。除了单核细胞,参与动脉粥样硬化不同阶段的其他先天免疫和非免疫细胞也可以发展出类似的记忆特征。这种机制为预防或治疗心血管疾病提供了令人兴奋的新的药理学靶点。