Li Wanling, Huang Yaqing, Liu Jun, Zhou Yue, Sun Hongyu, Fan Yonghong, Liu Feila
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China; The General Hospital of Western Theater Command, Chengdu 610083, China.
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China.
Life Sci. 2024 Dec 15;359:123204. doi: 10.1016/j.lfs.2024.123204. Epub 2024 Nov 2.
Atherosclerosis (AS) is a chronic inflammatory disease primarily affecting large and medium-sized arterial vessels, characterized by lipoprotein disorders, intimal thickening, smooth muscle cell proliferation, and the formation of vulnerable plaques. Macrophages (MΦs) play a vital role in the inflammatory response throughout all stages of atherosclerotic development and are considered significant therapeutic targets. In early lesions, macrophage efferocytosis rapidly eliminates harmful cells. However, impaired efferocytosis in advanced plaques perpetuates the inflammatory microenvironment of AS. Defective efferocytosis has emerged as a key factor in atherosclerotic pathogenesis and the progression to severe cardiovascular disease. Herein, this review probes into investigate the potential mechanisms at the cellular, molecular, and organelle levels underlying defective macrophage efferocytosis in advanced lesion plaques. In the inflammatory microenvironments of AS with interactions among diverse inflammatory immune cells, impaired macrophage efferocytosis is strongly linked to multiple factors, such as a lower absolute number of phagocytes, the aberrant expression of crucial molecules, and impaired mitochondrial energy provision in phagocytes. Thus, focusing on molecular targets to enhance macrophage efferocytosis or targeting mitochondrial therapy to restore macrophage metabolism homeostasis has emerged as a potential strategy to mitigate the progression of advanced atherosclerotic plaque, providing various treatment options.
动脉粥样硬化（AS）是一种主要影响大中型动脉血管的慢性炎症性疾病，其特征为脂蛋白紊乱、内膜增厚、平滑肌细胞增殖以及易损斑块的形成。巨噬细胞（MΦs）在动脉粥样硬化发展的各个阶段的炎症反应中起着至关重要的作用，被认为是重要的治疗靶点。在早期病变中，巨噬细胞胞葬作用能迅速清除有害细胞。然而，晚期斑块中胞葬作用受损会使AS的炎症微环境持续存在。有缺陷的胞葬作用已成为动脉粥样硬化发病机制及进展为严重心血管疾病的关键因素。在此，本综述探讨了晚期病变斑块中巨噬细胞胞葬作用缺陷在细胞、分子和细胞器水平的潜在机制。在AS的炎症微环境中，多种炎症免疫细胞相互作用，巨噬细胞胞葬作用受损与多种因素密切相关，如吞噬细胞绝对数量减少、关键分子的异常表达以及吞噬细胞线粒体能量供应受损。因此，专注于增强巨噬细胞胞葬作用的分子靶点或靶向线粒体治疗以恢复巨噬细胞代谢稳态已成为减轻晚期动脉粥样硬化斑块进展的潜在策略，提供了多种治疗选择。
