Reactive oxygen species in thoracic aortic dissection: Insights into mechanisms and disease progression

Thoracic aortic dissection (TAD) is a life-threatening vascular disorder defined by disruption of the aortic intima and progressive degeneration of the medial layer, accompanied with false lumen formation. Accumulating evidence supports a pivotal contribution of reactive oxygen species (ROS) to the initiation and progression of TAD, primarily by driving oxidative stress-associated cellular events. This review summarizes the ROS production mechanism in TAD pathogenesis and discusses how ROS contribute to disease progression through oxidative stress, inflammatory signaling, and structural degradation of the aortic wall. We further examine the multilayered regulatory networks governing ROS activity, including transcriptional and epigenetic regulation, metabolic reprogramming, that collectively shape vascular dysfunction in TAD. In addition, we discuss potential ROS-targeted therapeutic treatments, including inhibition of ROS-generating enzymes, enhancement of antioxidant systems, modulation of downstream signaling pathways, and correction of metabolic reprogramming. We also critically discuss the translational limitations of current redox-targeted approaches, emphasizing the lack of disease specificity, limited clinical validation, and the challenge of selectively suppressing pathological ROS. This review aims to synthesize current evidence linking ROS dysregulation to the onset and progression of TAD, while highlighting emerging therapeutic strategies and their potential clinical implications.