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Drummer Cth , Saaoud F , Shao Y , Sun Y , Xu K , Lu Y , Ni D , Atar D , Jiang X , Wang H , Yang X
Trained Immunity and Reactivity of Macrophages and Endothelial Cells
Arterioscler Thromb Vasc Biol. 2021 Mar;41(3) :1032-1046
PMID: 33380171    PMCID: PMC7904591   
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Innate immune cells can develop exacerbated immunologic response and long-term inflammatory phenotype following brief exposure to endogenous or exogenous insults, which leads to an altered response towards a second challenge after the return to a nonactivated state. This phenomenon is known as trained immunity (TI). TI is not only important for host defense and vaccine response but also for chronic inflammations such as cardiovascular and metabolic diseases such as atherosclerosis. TI can occur in innate immune cells such as monocytes/macrophages, natural killer cells, endothelial cells (ECs), and nonimmune cells, such as fibroblast. In this brief review, we analyze the significance of TI in ECs, which are also considered as innate immune cells in addition to macrophages. TI can be induced by a variety of stimuli, including lipopolysaccharides, BCG (bacillus Calmette-Guerin), and oxLDL (oxidized low-density lipoprotein), which are defined as risk factors for cardiovascular and metabolic diseases. Furthermore, TI in ECs is functional for inflammation effectiveness and transition to chronic inflammation. Rewiring of cellular metabolism of the trained cells takes place during induction of TI, including increased glycolysis, glutaminolysis, increased accumulation of tricarboxylic acid cycle metabolites and acetyl-coenzyme A production, as well as increased mevalonate synthesis. Subsequently, this leads to epigenetic remodeling, resulting in important changes in chromatin architecture that enables increased gene transcription and enhanced proinflammatory immune response. However, TI pathways and inflammatory pathways are separated to ensure memory stays when inflammation undergoes resolution. Additionally, reactive oxygen species play context-dependent roles in TI. Therefore, TI plays significant roles in EC and macrophage pathology and chronic inflammation. However, further characterization of TI in ECs and macrophages would provide novel insights into cardiovascular disease pathogenesis and new therapeutic targets. Graphic Abstract: A graphic abstract is available for this article.
1524-4636 Drummer, Charles 4th Saaoud, Fatma Shao, Ying Sun, Yu Xu, Keman Lu, Yifan Ni, Dong Atar, Diana Jiang, Xiaohua Wang, Hong Yang, Xiaofeng R01 HL138749/HL/NHLBI NIH HHS/United States R01 HL130233/HL/NHLBI NIH HHS/United States R01 HL131460/HL/NHLBI NIH HHS/United States R01 DK104116/DK/NIDDK NIH HHS/United States R01 HL132399/HL/NHLBI NIH HHS/United States R01 HL147565/HL/NHLBI NIH HHS/United States R01 DK113775/DK/NIDDK NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Review Arterioscler Thromb Vasc Biol. 2021 Mar;41(3):1032-1046. doi: 10.1161/ATVBAHA.120.315452. Epub 2020 Dec 31.