Singh Bandana, Li Kathryn, Cui Kui, Peng Qianman, Cowan Douglas B, Wang Da-Zhi, Chen Kaifu, Chen Hong
Vascular Biology Program, Department of Surgery, Harvard Medical School, Boston Children's Hospital, Boston, MA, United States.
Center for Regenerative Medicine, University of South Florida Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
Front Cardiovasc Med. 2022 Sep 30;9:1031293. doi: 10.3389/fcvm.2022.1031293. eCollection 2022.
The efficient phagocytic clearance of dying cells and apoptotic cells is one of the processes that is essential for the maintenance of physiologic tissue function and homeostasis, which is termed "efferocytosis." Under normal conditions, "find me" and "eat me" signals are released by apoptotic cells to stimulate the engulfment and efferocytosis of apoptotic cells. In contrast, abnormal efferocytosis is related to chronic and non-resolving inflammatory diseases such as atherosclerosis. In the initial steps of atherosclerotic lesion development, monocyte-derived macrophages display efficient efferocytosis that restricts plaque progression; however, this capacity is reduced in more advanced lesions. Macrophage reprogramming as a result of the accumulation of apoptotic cells and augmented inflammation accounts for this diminishment of efferocytosis. Furthermore, defective efferocytosis plays an important role in necrotic core formation, which triggers plaque rupture and acute thrombotic cardiovascular events. Recent publications have focused on the essential role of macrophage efferocytosis in cardiac pathophysiology and have pointed toward new therapeutic strategies to modulate macrophage efferocytosis for cardiac tissue repair. In this review, we discuss the molecular and cellular mechanisms that regulate efferocytosis in vascular cells, including macrophages and other phagocytic cells and detail how efferocytosis-related molecules contribute to the maintenance of vascular hemostasis and how defective efferocytosis leads to the formation and progression of atherosclerotic plaques.
死亡细胞和凋亡细胞的有效吞噬清除是维持生理组织功能和内环境稳定所必需的过程之一，这一过程被称为“胞葬作用”。在正常情况下，凋亡细胞会释放“找到我”和“吃掉我”信号，以刺激对凋亡细胞的吞噬和胞葬作用。相反，异常的胞葬作用与慢性和难以消退的炎症性疾病如动脉粥样硬化有关。在动脉粥样硬化病变发展的初始阶段，单核细胞衍生的巨噬细胞表现出有效的胞葬作用，可限制斑块进展；然而，在更晚期的病变中这种能力会降低。凋亡细胞的积累和炎症加剧导致巨噬细胞重编程，这解释了胞葬作用的减弱。此外，有缺陷的胞葬作用在坏死核心形成中起重要作用，坏死核心会引发斑块破裂和急性血栓性心血管事件。最近的出版物聚焦于巨噬细胞胞葬作用在心脏病理生理学中的重要作用，并指出了调节巨噬细胞胞葬作用以修复心脏组织的新治疗策略。在这篇综述中，我们讨论调节血管细胞（包括巨噬细胞和其他吞噬细胞）中胞葬作用的分子和细胞机制，并详细阐述与胞葬作用相关的分子如何有助于维持血管止血，以及有缺陷的胞葬作用如何导致动脉粥样硬化斑块的形成和进展。
