Department of Medicine (Cardiology), Albert Einstein College of Medicine, The Wilf Family Cardiovascular Research Institute, Bronx, New York.
Am J Physiol Cell Physiol. 2022 Oct 1;323(4):C1304-C1324. doi: 10.1152/ajpcell.00230.2022. Epub 2022 Sep 12.
The heart contains a population of resident macrophages that markedly expands following injury through recruitment of monocytes and through proliferation of macrophages. In myocardial infarction, macrophages have been implicated in both injurious and reparative responses. In coronary atherosclerotic lesions, macrophages have been implicated in disease progression and in the pathogenesis of plaque rupture. Following myocardial infarction, resident macrophages contribute to initiation and regulation of the inflammatory response. Phagocytosis and efferocytosis are major functions of macrophages during the inflammatory phase of infarct healing, and mediate phenotypic changes, leading to acquisition of an anti-inflammatory macrophage phenotype. Infarct macrophages respond to changes in the cytokine content and extracellular matrix composition of their environment and secrete fibrogenic and angiogenic mediators, playing a central role in repair of the infarcted heart. Macrophages may also play a role in scar maturation and may contribute to chronic adverse remodeling of noninfarcted segments. Single cell studies have revealed a remarkable heterogeneity of macrophage populations in infarcted hearts; however, the relations between transcriptomic profiles and functional properties remain poorly defined. This review manuscript discusses the fate, mechanisms of expansion and activation, and role of macrophages in the infarcted heart. Considering their critical role in injury, repair, and remodeling, macrophages are important, but challenging, targets for therapeutic interventions in myocardial infarction.
心脏内存在一群常驻巨噬细胞，这些细胞在损伤后会通过单核细胞的募集和巨噬细胞的增殖而显著扩增。在心肌梗死中，巨噬细胞被认为参与了损伤和修复反应。在冠状动脉粥样硬化病变中，巨噬细胞被认为参与了疾病进展和斑块破裂的发病机制。心肌梗死后，常驻巨噬细胞有助于炎症反应的启动和调节。吞噬作用和细胞外噬作用是梗死愈合炎症期巨噬细胞的主要功能，调节表型变化，导致获得抗炎性巨噬细胞表型。梗死巨噬细胞对细胞因子含量和细胞外基质组成的变化作出反应，并分泌成纤维细胞和血管生成介质，在梗死心脏的修复中发挥核心作用。巨噬细胞也可能在瘢痕成熟中发挥作用，并可能导致非梗死节段的慢性不良重塑。单细胞研究揭示了梗死心脏中巨噬细胞群体的显著异质性；然而，转录组谱和功能特性之间的关系仍未得到明确界定。这篇综述文章讨论了巨噬细胞在梗死心脏中的命运、扩增和激活机制以及作用。考虑到它们在损伤、修复和重塑中的关键作用，巨噬细胞是心肌梗死后治疗干预的重要但具有挑战性的靶点。
