Rochette Luc, Dogon Geoffrey, Rigal Eve, Zeller Marianne, Cottin Yves, Vergely Catherine
Équipe d'accueil (EA 7460) : physiopathologie et épidémiologie cérébro-cardiovasculaires (PEC2), faculté des sciences de santé, université de Bourgogne-Franche-Comté, 7, boulevard Jeanne-d'Arc, 21000 Dijon, France.
Équipe d'accueil (EA 7460) : physiopathologie et épidémiologie cérébro-cardiovasculaires (PEC2), faculté des sciences de santé, université de Bourgogne-Franche-Comté, 7, boulevard Jeanne-d'Arc, 21000 Dijon, France.
Arch Cardiovasc Dis. 2023 Oct;116(10):474-484. doi: 10.1016/j.acvd.2023.07.007. Epub 2023 Aug 18.
In an adult human, billions of cells die and turn over daily. During this process, many apoptotic cells are produced and subsequently cleared by phagocytes - a process termed efferocytosis, which plays a critical role in tissue homeostasis. Efferocytosis is an important mechanism in the control of inflammatory processes. Efficient efferocytosis inhibits accumulation of apoptotic cells/debris and maintains homeostasis before the onset of necrosis (secondary necrosis), which promotes inflammation or injury. During efferocytosis, mitochondrial fission and the oxidative stress process are linked through reactive oxygen species production and oxidative stress control. Autophagy plays an important role in inhibiting inflammation and apoptosis, and in promoting efferocytosis by activated inflammatory cells, particularly neutrophils and macrophages. Autophagy in neutrophils is activated by phagocytosis of pathogens or activation of pattern recognition receptors. Autophagy is essential for major neutrophil functions, including degranulation, reactive oxygen species production, oxidative stress and release of neutrophil extracellular cytokines. Failed efferocytosis is a key mechanism driving the development and progression of chronic inflammatory diseases, including atherosclerosis, cardiometabolic pathology, neurodegenerative disease and cancer. Impairment of efferocytosis in apoptotic macrophages is a determinant of atherosclerosis severity and the vulnerability of plaques to rupture. Recent results suggest that inhibition of efferocytosis in the protection of the myocardium results in reduced infiltration of reparatory macrophages into the tissue, in association with oxidative stress reduction. Activated macrophages play a central role in the development and resolution of inflammation. The resolution of inflammation through efferocytosis is an endogenous process that protects host tissues from prolonged or excessive inflammation. Accordingly, therapeutic strategies that ameliorate efferocytosis control would be predicted to dampen inflammation and improve resolution. Thus, therapies targeting efferocytosis will provide a new means of treating and preventing cardiovascular and metabolic diseases involving the chronic inflammatory state.
在成年人体内，数十亿细胞每天都会死亡并更新换代。在此过程中，会产生许多凋亡细胞，随后被吞噬细胞清除，这一过程称为胞葬作用，它在组织稳态中起着关键作用。胞葬作用是控制炎症过程的重要机制。高效的胞葬作用可抑制凋亡细胞/碎片的积累，并在坏死（继发性坏死）发生之前维持稳态，而坏死会促进炎症或损伤。在胞葬作用过程中，线粒体分裂和氧化应激过程通过活性氧的产生和氧化应激控制相互关联。自噬在抑制炎症和凋亡以及促进活化的炎症细胞（特别是中性粒细胞和巨噬细胞）的胞葬作用方面发挥着重要作用。中性粒细胞中的自噬通过病原体的吞噬作用或模式识别受体的激活而被激活。自噬对于中性粒细胞的主要功能至关重要，包括脱颗粒、活性氧的产生、氧化应激以及中性粒细胞胞外细胞因子的释放。胞葬作用失败是驱动慢性炎症性疾病（包括动脉粥样硬化、心脏代谢病理学、神经退行性疾病和癌症）发展和进展的关键机制。凋亡巨噬细胞中胞葬作用的受损是动脉粥样硬化严重程度和斑块易破裂性的决定因素。最近的结果表明，在心肌保护中抑制胞葬作用会导致修复性巨噬细胞向组织中的浸润减少，并伴有氧化应激的降低。活化的巨噬细胞在炎症的发展和消退中起着核心作用。通过胞葬作用实现的炎症消退是一个内源性过程，可保护宿主组织免受长期或过度炎症的影响。因此，可以预测，改善胞葬作用控制的治疗策略将减轻炎症并改善炎症消退。因此，针对胞葬作用的疗法将为治疗和预防涉及慢性炎症状态的心血管和代谢疾病提供一种新方法。
