Department of Medicine, Marc and Ruti Bell Program for Vascular Biology and Disease, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY, USA.
Department of Medicine, Heart Institute & Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Nat Immunol. 2018 Jun;19(6):526-537. doi: 10.1038/s41590-018-0113-3. Epub 2018 May 18.
After activation, cells of the myeloid lineage undergo robust metabolic transitions, as well as discrete epigenetic changes, that can dictate both ongoing and future inflammatory responses. In atherosclerosis, in which macrophages play central roles in the initiation, growth, and ultimately rupture of arterial plaques, altered metabolism is a key feature that dictates macrophage function and subsequent disease progression. This Review explores how factors central to the plaque microenvironment (for example, altered cholesterol metabolism, oxidative stress, hypoxia, apoptotic and necrotic cells, and hyperglycemia) shape the metabolic rewiring of macrophages in atherosclerosis as well as how these metabolic shifts in turn alter macrophage immune-effector and tissue-reparative functions. Finally, this overview offers insight into the challenges and opportunities of harnessing metabolism to modulate aberrant macrophage responses in disease.
激活后，髓系细胞经历强烈的代谢转变以及离散的表观遗传变化，这些变化可以决定持续和未来的炎症反应。在动脉粥样硬化中，巨噬细胞在动脉斑块的起始、生长和最终破裂中发挥核心作用，改变代谢是决定巨噬细胞功能和随后疾病进展的关键特征。本综述探讨了斑块微环境中的关键因素（例如，胆固醇代谢改变、氧化应激、缺氧、凋亡和坏死细胞以及高血糖）如何塑造动脉粥样硬化中巨噬细胞的代谢重编程，以及这些代谢变化如何反过来改变巨噬细胞免疫效应和组织修复功能。最后，本文概述了利用代谢来调节疾病中异常的巨噬细胞反应所面临的挑战和机遇。
