细胞程序性死亡在主动脉瘤和主动脉夹层中的研究进展

Advances in programmed cell death of aortic aneurysm and aortic dissection

摘要:

主动脉瘤(AA)和主动脉夹层(AD)属于心血管疾病的危重急症,严重威胁人类生命健康。各种因素导致主动脉壁中的平滑肌细胞等各类细胞进行性减少是AA和AD发生的重要机制,AD通常是在高血压等机械压力诱导下导致受损内膜出现破口或主动脉壁内发生出血,而AA则是在长时间血流冲击等刺激下导致主动脉壁变薄并向外膨出。目前,越来越多的证据显示,细胞凋亡、坏死性凋亡、焦亡、铁死亡、铜死亡、多腺苷二磷酸核糖聚合酶1(PARP-1)依赖性细胞死亡以及免疫原性细胞死亡等多种细胞程序性死亡方式,在AA和AD的发病机制中扮演着关键角色。因此,从细胞程序性死亡的角度深入理解AA与AD发病的关键分子和途径,并寻找抑制这些程序性死亡方式的药物,对于预防主动脉损伤和阻止疾病进展至关重要。该文综述了多种细胞程序性死亡方式在AA和AD发生发展过程中的作用及其研究进展,明确了细胞程序性死亡在AA和AD形成中的核心地位,并为临床寻找新的治疗方法提供了思路。

Abstract:

Aortic aneurysm (AA) and aortic dissection (AD) are critical cardiovascular disease emergencies that seriously threaten human life and health. Due to various factors, the progressive reduction of various types of cells, such as smooth muscle cells and endothelial cells in the aortic wall, is an essential mechanism for developing AA and AD. On this basis, AD is induced by mechanical stresses such as hypertension, leading to damaged endothelial rupture or hemorrhage within the aortic wall. However, AA causes the aortic wall to thin and expand outward in response to stimuli such as prolonged blood flow impingement. At present, increasing evidence shows that various programmed cell death, such as apoptosis, necroptosis, pyroptosis, ferroptosis, copper death, poly ADP-ribose polymerase 1 (PARP-1)-dependent cell death, and immunogenic cell death, play essential roles in the pathogenesis of AA and AD. Therefore, understanding the key molecules and pathways in the pathogenesis of AA and AD from the perspective of programmed cell death and searching for inhibitors of various types of programmed death is essential to prevent aortic destruction and disease progression. The review summarizes the roles and research progress of different types of programmed cell death modalities in the development of AA and AD, clarifies the central position of programmed cell death in forming AA and AD, and searches for new therapeutic methods for the clinic.