State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, State Key Laboratory of Component-based Chinese Medicine, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Heart center, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.
Cell Signal. 2024 Nov;123:111370. doi: 10.1016/j.cellsig.2024.111370. Epub 2024 Aug 30.
Acute myocardial infarction (AMI) is the leading cause of death worldwide, and reperfusion therapy is a critical therapeutic approach to reduce myocardial ischemic injury and minimize infarct size. However, ischemia/reperfusion (I/R) itself also causes myocardial injury, and inflammation is an essential mechanism by which it leads to myocardial injury, with macrophages as crucial immune cells in this process. Macrophages are innate immune cells that maintain tissue homeostasis, host defence during pathogen infection, and repair during tissue injury. During the acute phase of I/R, M1-type macrophages generate a pro-inflammatory milieu, clear necrotic myocardial tissue, and further recruit mononuclear (CCR2) macrophages. Over time, the reparative (M2 type) macrophages gradually became dominant. In recent years, metabolic studies have shown a clear correlation between the metabolic profile of macrophages and their phenotype and function. M1-type macrophages are mainly characterized by glycolytic energy supply, and their tricarboxylic acid (TCA) cycle and mitochondrial oxidative phosphorylation (OXPHOS) processes are impaired. In contrast, M2 macrophages rely primarily on OXPHOS for energy. Changing the metabolic profile of macrophages can alter the macrophage phenotype. Altered energy pathways are also present in macrophages during I/R, and intervention in this process contributes to earlier and greater M2 macrophage infiltration, which may be a potential target for the treatment of myocardial I/R injury. Therefore, this paper mainly reviews the characteristics of macrophage energy metabolism alteration and phenotypic transition during I/R and its mechanism of mediating myocardial injury to provide a basis for further research in this field.
急性心肌梗死（AMI）是全球范围内导致死亡的主要原因，再灌注治疗是减少心肌缺血损伤和最小化梗死面积的关键治疗方法。然而，缺血/再灌注（I/R）本身也会导致心肌损伤，炎症是导致心肌损伤的重要机制，巨噬细胞在这个过程中是至关重要的免疫细胞。巨噬细胞是先天免疫细胞，它们在组织稳态、病原体感染期间的宿主防御以及组织损伤期间的修复中发挥作用。在 I/R 的急性期，M1 型巨噬细胞产生促炎环境，清除坏死的心肌组织，并进一步招募单核细胞（CCR2）巨噬细胞。随着时间的推移，修复型（M2 型）巨噬细胞逐渐占主导地位。近年来，代谢研究表明巨噬细胞的代谢特征与其表型和功能之间存在明显的相关性。M1 型巨噬细胞主要以糖酵解供能为特征，其三羧酸（TCA）循环和线粒体氧化磷酸化（OXPHOS）过程受损。相比之下，M2 巨噬细胞主要依赖 OXPHOS 供能。改变巨噬细胞的代谢特征可以改变巨噬细胞的表型。在 I/R 期间，巨噬细胞中也存在改变的能量途径，干预这个过程有助于更早和更大程度地浸润 M2 巨噬细胞，这可能是治疗心肌 I/R 损伤的一个潜在靶点。因此，本文主要综述了 I/R 期间巨噬细胞能量代谢改变和表型转化的特征及其介导心肌损伤的机制，为该领域的进一步研究提供依据。
