Tabas Ira, Lichtman Andrew H
Departments of Medicine, Physiology, and Pathology & Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Immunity. 2017 Oct 17;47(4):621-634. doi: 10.1016/j.immuni.2017.09.008.
Atherosclerosis is an arterial disease process characterized by the focal subendothelial accumulation of apolipoprotein-B-containing lipoproteins, immune and vascular wall cells, and extracellular matrix. The lipoproteins acquire features of damage-associated molecular patterns and trigger first an innate immune response, dominated by monocyte-macrophages, and then an adaptive immune response. These inflammatory responses often become chronic and non-resolving and can lead to arterial damage and thrombosis-induced organ infarction. The innate immune response is regulated at various stages, from hematopoiesis to monocyte changes and macrophage activation. The adaptive immune response is regulated primarily by mechanisms that affect the balance between regulatory and effector T cells. Mechanisms related to cellular cholesterol, phenotypic plasticity, metabolism, and aging play key roles in affecting these responses. Herein, we review select topics that shed light on these processes and suggest new treatment strategies.
动脉粥样硬化是一种动脉疾病过程,其特征在于含载脂蛋白B的脂蛋白、免疫细胞和血管壁细胞以及细胞外基质在血管内膜下局灶性积聚。这些脂蛋白具有损伤相关分子模式的特征,首先引发以单核细胞-巨噬细胞为主导的先天性免疫反应,然后引发适应性免疫反应。这些炎症反应通常会变得慢性且无法消退,并可能导致动脉损伤和血栓形成诱导的器官梗死。先天性免疫反应在从造血到单核细胞变化和巨噬细胞激活的各个阶段受到调节。适应性免疫反应主要由影响调节性T细胞和效应性T细胞之间平衡的机制调节。与细胞胆固醇、表型可塑性、代谢和衰老相关的机制在影响这些反应中起关键作用。在此,我们综述了一些有助于阐明这些过程的选定主题,并提出了新的治疗策略。