Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
J Clin Invest. 2022 May 2;132(9). doi: 10.1172/JCI157011.
Cardiovascular disease (CVD) accounts for almost half of all deaths related to non-communicable disease worldwide, making it the single largest global cause of mortality. Although the risk factors for coronary artery disease - the most common cause of CVD - are well known and include hypertension, high cholesterol, age, and genetics, CVDs are now recognized as chronic inflammatory conditions. Arterial blockages, known as atherosclerosis, develop due to excess cholesterol accumulating within the arterial wall, creating a perpetually inflammatory state. The normally quiescent intimal layer of the vessel wall becomes laden with inflammatory cells, which alters the surrounding endothelial, smooth muscle, and extracellular matrix components to propagate disease. Macrophages, which can be either tissue resident or monocyte derived, are a key player in atherosclerotic disease progression and regression, and the understanding of their functions and origins continues to evolve with the use of deep phenotyping methodologies. This Review outlines how macrophages interact with each layer of the developing atherosclerotic plaque and discusses new concepts that are challenging our previous views on how macrophages function and our evolving understanding of the contribution of macrophages to disease.
心血管疾病（CVD）占全球与非传染性疾病相关死亡人数的近一半，是全球死亡的最大单一原因。虽然冠状动脉疾病（CVD 最常见的病因）的危险因素已广为人知，包括高血压、高胆固醇、年龄和遗传因素，但 CVD 现在被认为是慢性炎症性疾病。动脉阻塞，称为动脉粥样硬化，是由于动脉壁内胆固醇积聚过多而导致的，从而产生持续的炎症状态。血管壁的正常静止内膜层充满了炎症细胞，这会改变周围的内皮细胞、平滑肌和细胞外基质成分，从而导致疾病的发生。巨噬细胞可以是组织驻留的，也可以是单核细胞衍生的，是动脉粥样硬化疾病进展和消退的关键参与者，随着深度表型分析方法的使用，对其功能和来源的理解仍在不断发展。这篇综述概述了巨噬细胞如何与正在发展的动脉粥样硬化斑块的每一层相互作用，并讨论了新的概念，这些概念正在挑战我们以前对巨噬细胞功能的看法，以及我们对巨噬细胞在疾病中的作用的不断发展的理解。
