Zhang Bingtao, Zou Yan, Yuan Zixuan, Jiang Kun, Zhang Zhaoxiang, Chen Shujuan, Zhou Xiaoming, Wu Qi, Zhang Xin
Department of Neurosurgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Department of Neurosurgery, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Front Immunol. 2024 Nov 26;15:1485222. doi: 10.3389/fimmu.2024.1485222. eCollection 2024.
Cardiovascular and cerebrovascular diseases have surpassed cancer as significant global health challenges, which mainly include atherosclerosis, myocardial infarction, hemorrhagic stroke and ischemia stroke. The inflammatory response immediately following these diseases profoundly impacts patient prognosis and recovery. Efficient resolution of inflammation is crucial not only for halting the inflammatory process but also for restoring tissue homeostasis. Efferocytosis, the phagocytic clearance of dying cells by phagocytes, especially microglia and macrophages, plays a critical role in this resolution process. Upon tissue injury, phagocytes are recruited to the site of damage where they engulf and clear dying cells through efferocytosis. Efferocytosis suppresses the secretion of pro-inflammatory cytokines, stimulates the production of anti-inflammatory cytokines, modulates the phenotype of microglia and macrophages, accelerates the resolution of inflammation, and promotes tissue repair. It involves three main stages: recognition, engulfment, and degradation of dying cells. Optimal removal of apoptotic cargo by phagocytes requires finely tuned machinery and associated modifications. Key molecules in efferocytosis, such as 'Find-me signals', 'Eat-me signals', and 'Don't eat-me signals', have been shown to enhance efferocytosis following cardiovascular and cerebrovascular diseases. Moreover, various additional molecules, pathways, and mitochondrial metabolic processes have been identified to enhance prognosis and outcomes via efferocytosis in diverse experimental models. Impaired efferocytosis can lead to inflammation-associated pathologies and prolonged recovery periods. Therefore, this review consolidates current understanding of efferocytosis mechanisms and its application in cardiovascular and cerebrovascular diseases, proposing future research directions.
心血管疾病和脑血管疾病已超越癌症，成为重大的全球健康挑战，主要包括动脉粥样硬化、心肌梗死、出血性卒中和缺血性卒中。这些疾病发生后立即出现的炎症反应对患者的预后和恢复有深远影响。有效解决炎症不仅对阻止炎症过程至关重要，而且对恢复组织内环境稳定也至关重要。胞葬作用，即吞噬细胞（尤其是小胶质细胞和巨噬细胞）对死亡细胞的吞噬清除，在这个解决过程中起关键作用。组织损伤时，吞噬细胞被招募到损伤部位，在那里它们通过胞葬作用吞噬并清除死亡细胞。胞葬作用抑制促炎细胞因子的分泌，刺激抗炎细胞因子的产生，调节小胶质细胞和巨噬细胞的表型，加速炎症的消退，并促进组织修复。它包括三个主要阶段：死亡细胞的识别、吞噬和降解。吞噬细胞对凋亡物质的最佳清除需要精细调节的机制和相关修饰。胞葬作用中的关键分子，如“找我信号”、“吃我信号”和“别吃我信号”，已被证明可增强心血管疾病和脑血管疾病后的胞葬作用。此外，在各种实验模型中，已确定了各种其他分子、途径和线粒体代谢过程，可通过胞葬作用改善预后和结果。胞葬作用受损可导致炎症相关病理和恢复期延长。因此，本综述巩固了目前对胞葬作用机制及其在心血管疾病和脑血管疾病中的应用的理解，提出了未来的研究方向。
