Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
Pharmacol Res. 2021 Aug;170:105699. doi: 10.1016/j.phrs.2021.105699. Epub 2021 Jun 2.
Phagocytic clearance of dead cells and debris is critical for inflammation resolution and maintenance of tissue homeostasis. Consequently, defective clearance of dead cells and debris is associated with initiation and exacerbation of several autoimmune disorders and chronic inflammatory diseases such as atherosclerosis. The progressive loss of dead cell clearance capacity within the atherosclerotic plaque leads to accumulation of necrotic cells, chronic non-resolving inflammation, and expansion of the necrotic core, which triggers atherosclerotic plaque rupture and clinical manifestation of acute thrombotic cardiovascular adverse events. In this review, we describe the fundamental molecular and cellular mechanisms of dead cell clearance and how it goes awry in atherosclerosis. Finally, we highlight novel therapeutic strategies that enhance dead cell and debris clearance within the atherosclerotic plaque to promote inflammation resolution and atherosclerotic plaque stabilization.
吞噬细胞清除死亡细胞和细胞碎片对于炎症的消退和组织的稳态维持至关重要。因此，死亡细胞和细胞碎片清除功能缺陷与几种自身免疫性疾病和慢性炎症性疾病（如动脉粥样硬化）的发生和恶化有关。动脉粥样硬化斑块内清除死亡细胞能力的逐渐丧失会导致坏死细胞的堆积、慢性非解决性炎症以及坏死核心的扩大，从而引发动脉粥样硬化斑块破裂和急性血栓性心血管不良事件的临床表现。在这篇综述中，我们描述了死亡细胞清除的基本分子和细胞机制，以及其在动脉粥样硬化中的异常情况。最后，我们强调了一些新的治疗策略，这些策略可以增强动脉粥样硬化斑块内的死亡细胞和细胞碎片的清除，从而促进炎症的消退和动脉粥样硬化斑块的稳定。
