Kojima Yoko, Weissman Irving L, Leeper Nicholas J
From Department of Surgery, Division of Vascular Surgery (Y.K., N.J.L.), Institute for Stem Cell Biology and Regenerative Medicine (I.L.W.), and Department of Medicine, Division of Cardiovascular Medicine (N.J.L.), Stanford University School of Medicine, CA.
Circulation. 2017 Jan 31;135(5):476-489. doi: 10.1161/CIRCULATIONAHA.116.025684.
The necrotic core has long been a hallmark of the vulnerable atherosclerotic plaque. Although apoptotic cells are cleared quickly in almost all other tissue beds, their removal appears to be significantly impaired in the diseased blood vessel. Emerging evidence indicates that this phenomenon is caused by a defect in efferocytosis, the process by which apoptotic tissue is recognized for engulfment by phagocytic cells such as macrophages. Genetic and experimental data suggest that efferocytosis is impaired during atherogenesis caused by dysregulation of so-called eat me ligands, which govern the edibility of cells undergoing programmed cell death. The following is a summary of recent data indicating that efferocytosis is a major unappreciated driver of lesion expansion but also a reversible defect that can potentially be targeted as a means to prevent plaque progression.
坏死核心长期以来一直是易损动脉粥样硬化斑块的一个标志。尽管凋亡细胞在几乎所有其他组织床中都能迅速清除,但在病变血管中其清除似乎明显受损。新出现的证据表明,这种现象是由吞噬作用缺陷引起的,吞噬作用是指凋亡组织被巨噬细胞等吞噬细胞识别并吞噬的过程。遗传和实验数据表明,在动脉粥样硬化形成过程中,由于所谓的“吃我”配体失调,吞噬作用受损,这些配体决定了正在经历程序性细胞死亡的细胞的可吞噬性。以下是近期数据的总结,这些数据表明吞噬作用是病变扩展的一个主要未被重视的驱动因素,但也是一个可逆性缺陷,有可能作为预防斑块进展的一种手段加以靶向治疗。