From the Department of Cardiovascular Medicine, the First Affiliated Hospital, Xi'an Jiaotong University, Shaanxi, P.R. China (L.S., Z.Y.).
Center for Metabolic Disease Research (L.S., X.Y., H.W.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Arterioscler Thromb Vasc Biol. 2020 Sep;40(9):1990-2001. doi: 10.1161/ATVBAHA.120.314037. Epub 2020 Jul 23.
Innate and adaptive immunity participate in and regulate numerous human diseases. Increasing evidence implies that metabolic reprogramming mediates immune cell functional changes during immune responses. In this review, we present and discuss our current understanding of metabolic regulation in different immune cells and their subsets in response to pathological stimuli. An interactive biochemical and molecular model was established to characterize metabolic reprogramming and their functional implication in anti-inflammatory, immune resolution, and proinflammatory responses. We summarize 2 major features of metabolic reprogramming in inflammatory stages in innate and adaptive immune cells: (1) energy production and biosynthesis reprogramming, including increased glycolysis and decreased oxidative phosphorylation, to secure faster ATP production and biosynthesis for defense response and damage repair and (2) epigenetic reprogramming, including enhanced histone acetylation and suppressed DNA methylation, due to altered accessibility of acetyl/methyl group donor and metabolite-modulated enzymatic activity. Finally, we discuss current strategies of metabolic and epigenetic therapy in cardiovascular disease and recommend cell-specific metabolic and gene-targeted site-specific epigenetic alterations for future therapies.
先天免疫和适应性免疫参与并调节多种人类疾病。越来越多的证据表明，代谢重编程介导免疫细胞在免疫反应过程中的功能变化。在这篇综述中，我们介绍并讨论了我们目前对不同免疫细胞及其亚群在应对病理刺激时的代谢调控的理解。建立了一个交互式生化和分子模型，以描述代谢重编程及其在抗炎、免疫缓解和促炎反应中的功能意义。我们总结了先天免疫和适应性免疫细胞在炎症阶段代谢重编程的 2 个主要特征：(1)能量产生和生物合成重编程，包括增加糖酵解和减少氧化磷酸化，以确保更快的 ATP 产生和生物合成，用于防御反应和损伤修复；(2)表观遗传重编程，包括增强组蛋白乙酰化和抑制 DNA 甲基化，这是由于乙酰基/甲基供体的可及性改变和代谢物调节的酶活性改变所致。最后，我们讨论了代谢和表观遗传治疗在心血管疾病中的当前策略，并为未来的治疗推荐了细胞特异性代谢和基因靶向的特定表观遗传改变。
