Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, CA (K.-U.J., Y.K., N.J.L.).
Stanford Institute for Stem Cell Biology and Regenerative Medicine (I.L.W.), Stanford University, CA.
Arterioscler Thromb Vasc Biol. 2022 Jun;42(6):e145-e154. doi: 10.1161/ATVBAHA.122.317049. Epub 2022 Apr 7.
A key feature of atherogenesis is the accumulation of diseased and dying cells within the lesional necrotic core. While the burden of intraplaque apoptotic cells may be driven in part by an increase in programmed cell death, mounting evidence suggests that their presence may primarily be dictated by a defect in programmed cell removal, or efferocytosis. In this brief review, we will summarize the evidence suggesting that inflammation-dependent changes within the plaque render target cells inedible and reduce the appetite of lesional phagocytes. We will present the genetic causation studies, which indicate these phenomena promote lesion expansion and plaque vulnerability, and the interventional data which suggest that these processes can be reversed. Particular emphasis is provided related to the antiphagocytic CD47 (cluster of differentiation 47) do not eat me axis, which has emerged as a novel antiatherosclerotic translational target that is predicted to provide benefit independent of traditional cardiovascular risk factors.
动脉粥样硬化形成的一个关键特征是病变坏死核心内病变和垂死细胞的积累。虽然斑块内凋亡细胞的负担可能部分是由程序性细胞死亡的增加所驱动,但越来越多的证据表明,它们的存在主要可能是由于程序性细胞清除或吞噬作用的缺陷所致。在这篇简短的综述中,我们将总结表明斑块内炎症依赖性变化使靶细胞变得不可食用并降低病变吞噬细胞食欲的证据。我们将介绍表明这些现象促进病变扩展和斑块脆弱性的遗传因果关系研究,以及表明这些过程可以逆转的干预数据。特别强调了抗吞噬性 CD47(分化群 47)“不要吃我”轴,该轴已成为一种新的抗动脉粥样硬化转化靶点,预计可提供独立于传统心血管危险因素的益处。