Discipline of Pathology and Charles Perkins Centre, The University of Sydney, Sydney, Australia.
Cardiology Department, Royal Prince Alfred Hospital, Sydney, Australia.
Redox Rep. 2021 Dec;26(1):45-52. doi: 10.1080/13510002.2021.1899473.
The primary objective of this review was to explore the contribution of oxidative stress to the pathogenesis of genetically-triggered thoracic aortic aneurysm (TAA). Genetically-triggered TAAs manifest substantial variability in onset, progression, and risk of aortic dissection, posing a significant clinical management challenge. There is a need for non-invasive biomarkers that predict the natural course of TAA and therapeutics that prevent aneurysm progression. An online systematic search was conducted within PubMed, MEDLINE, Scopus and ScienceDirect databases using keywords including: oxidative stress, ROS, nitrosative stress, genetically triggered thoracic aortic aneurysm, aortic dilatation, aortic dissection, Marfan syndrome, Bicuspid Aortic Valve, familial TAAD, Loeys Dietz syndrome, and Ehlers Danlos syndrome. There is extensive evidence of oxidative stress and ROS imbalance in genetically triggered TAA. Sources of ROS imbalance are variable but include dysregulation of redox mediators leading to either insufficient ROS removal or increased ROS production. Therapeutic exploitation of redox mediators is being explored in other cardiovascular conditions, with potential application to TAA warranting further investigation. Oxidative stress occurs in genetically triggered TAA, but the precise contribution of ROS to pathogenesis remains incompletely understood. Further research is required to define causative pathological relationships in order to develop therapeutic options.
本综述的主要目的是探讨氧化应激在遗传性胸主动脉瘤（TAA）发病机制中的作用。遗传性 TAA 的发病、进展和主动脉夹层风险存在显著的个体差异，这给临床管理带来了巨大挑战。因此，我们需要寻找能够预测 TAA 自然病程的非侵入性生物标志物和预防动脉瘤进展的治疗方法。我们在 PubMed、MEDLINE、Scopus 和 ScienceDirect 数据库中使用了“氧化应激”“ROS”“硝化应激”“遗传性胸主动脉瘤”“主动脉扩张”“主动脉夹层”“马凡综合征”“二叶式主动脉瓣”“家族性胸主动脉瘤”“Loeys-Dietz 综合征”和“埃勒斯-当洛斯综合征”等关键词进行了在线系统检索。有大量证据表明，氧化应激和 ROS 失衡与遗传性 TAA 有关。ROS 失衡的来源各不相同，但包括氧化还原调节剂的失调，导致 ROS 清除不足或产生增加。目前正在其他心血管疾病中探索氧化还原调节剂的治疗应用，其在 TAA 中的潜在应用值得进一步研究。氧化应激发生在遗传性 TAA 中，但 ROS 对发病机制的确切贡献仍不完全清楚。需要进一步研究以确定因果病理关系，从而开发治疗选择。
