血管老化在腹主动脉瘤发病中的作用及潜在的治疗靶点

Role of Vascular Aging in the Pathogenesis of Abdominal Aortic Aneurysm and Potential Therapeutic Targets

腹主动脉瘤是老年人中常见的主动脉退行性疾病,随着人口老龄化的进展,其发病率逐渐增高。然而,目前尚无特定的药物可以治愈或延缓腹主动脉瘤的扩张,动脉瘤一旦破裂患者死亡率接近90%,严重威胁患者生命健康。鉴于腹主动脉瘤在老年人群中的高发病率,本文将从血管老化的角度讨论衰老在腹主动脉瘤发病中的作用,包括慢性炎症、氧化应激、线粒体功能障碍、蛋白质稳态失衡、凋亡和坏死增加、细胞外基质重塑、营养感应失调、表观遗传改变、促衰老因子增加等,并列举一些腹主动脉瘤衰老相关的潜在药物靶点。本文将为腹主动脉瘤发病机制、药物研发、生物标志物等转化研究提供新思路。

Abdominal aortic aneurysm(AAA)is a common aortic degenerative disease in the elderly,and its incidence is gradually increasing with the aging of the population.There are no specific drugs available to delay the expansion of AAA.Once the aneurysm ruptures,the mortality will exceed 90%,which seriously threatens the life of patients.Given the high incidence of AAA in the elderly,this review discusses the role of vascular aging in the pathogenesis of AAA,involving chronic inflammation,oxidative stress,mitochondrial dysfunction,protein homeostasis imbalance,increased apoptosis and necrosis,extracellular matrix remodeling,nutritional sensing disorders,epigenetic changes,and increased pro-aging factors.Meanwhile,several potential aging-related drug targets of AAA are listed.This review provides new ideas for basic and translational medical research of AAA.