腹主动脉瘤中血管平滑肌细胞功能:现状与挑战

Vascular smooth muscle cell function in abdominal aortic aneurysm:current understanding and challenges

摘要:

腹主动脉瘤是一种以腹主动脉局部扩张为特征的严重血管疾病,其发病机制复杂,涉及慢性炎症、细胞外基质降解及血管细胞稳态失衡等多个环节,目前临床上仍缺乏能有效延缓或逆转其进展的药物治疗策略。血管平滑肌细胞作为主动脉中膜的主要细胞成分,其功能失调在腹主动脉瘤的发生与发展过程中起着核心作用。该综述系统阐述了血管平滑肌细胞在腹主动脉瘤中的关键病理生理过程,包括细胞衰老、表型转换、多种程序性死亡方式(包括凋亡、焦亡及铁死亡)、机械感知异常及其介导的细胞外基质降解。在此基础上,进一步探讨了靶向血管平滑肌细胞衰老、死亡及表型重塑等环节的潜在治疗策略。最后,该综述对该领域未来的研究方向进行了展望,以期为腹主动脉瘤的机制研究与防治提供新的思路和理论依据。

Abstract:

Abdominal aortic aneurysm is a severe vascular disease characterized by localized dilation of the abdominal aorta, with a complex pathogenesis involving multiple processes such as chronic inflammation, degradation of the extracellular matrix, and imbalance in vascular cell homeostasis. Currently, there is a lack of effective drug treatment strategies in clinical practice to delay or reverse its progression. Vascular smooth muscle cells, as the main cellular component of the aortic media, play a central role in the development and progression of abdominal aortic aneurysm through their dysfunctional state. This review systematically elaborates on the key pathophysiological processes of vascular smooth muscle cells in abdominal aortic aneurysm, including cellular senescence, phenotypic switching, various forms of programmed cell death (including apoptosis, pyroptosis and ferroptosis), impaired mechanosensing, and their mediated degradation of the extracellular matrix. Building on this, this review further discusses potential therapeutic strategies targeting vascular smooth muscle cell senescence, death, and phenotypic remodeling. Finally, this review provides prospects for future research directions in this field, aiming to provide new ideas and theoretical basis for the mechanism research and prevention of abdominal aortic aneurysm.