From the Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Canada; and University of Ottawa Heart Institute, Canada.
Arterioscler Thromb Vasc Biol. 2017 Jul;37(7):e75-e81. doi: 10.1161/ATVBAHA.117.309229.
Atherosclerotic vascular disease results from an imbalance of inflammatory and vascular cell accumulation and removal in the neointimal space. When pathways that promote cell recruitment, survival and proliferation are favored over to those that activate cell death, egress and clearance, the plaque expands. In contrast, programmed cell death and the efficient clearance of apoptotic bodies by efferocytosis reduces lesion cellularity and promotes a reparative environment and lesion stability. However, should these carefully balanced pathways become disturbed, lesions can accumulate cell debris, damaged-associated molecular patterns and arrested macrophages, all contributing to the pro-inflammatory environment and lesion instability. Here, we will review the latest understanding of how cell death in the vessel wall directly coordinates the development of atherosclerosis, and what molecular signals are orchestrating these pathways. We will discuss the necessity of cell death, and the ways in which the execution of different forms of cell death can direct different outcomes in the plaque, and how promoting the effective clearance of dead cells from the lesion is looking like a promising therapeutic path forward.
动脉粥样硬化血管疾病是由于新生内膜空间中炎症和血管细胞的积累和清除失衡所致。当促进细胞募集、存活和增殖的途径超过激活细胞死亡、迁出和清除的途径时，斑块就会扩大。相反，程序性细胞死亡和通过噬作用有效清除凋亡小体可减少病变细胞的数量，并促进修复环境和病变的稳定性。然而，如果这些精心平衡的途径受到干扰，病变可能会积累细胞碎片、损伤相关分子模式和被捕获的巨噬细胞，所有这些都会导致促炎环境和病变不稳定。在这里，我们将回顾最新的研究进展，了解血管壁中的细胞死亡如何直接协调动脉粥样硬化的发展，以及哪些分子信号在协调这些途径。我们将讨论细胞死亡的必要性，以及不同形式的细胞死亡如何在斑块中产生不同的结果，以及促进从病变中有效清除死亡细胞的方法，这些都有望成为一种有前途的治疗途径。
