Molecular mechanisms of programmed cell death in aortic dissection and advances in clinical translation

Aortic dissection (AD) is an acute cardiovascular emergency characterized by rapid progression and an extremely high risk of mortality. Its fundamental pathological process begins with an intimal tear, through which blood enters the medial layer to form a false lumen, leading to structural destabilization of the aortic wall, impaired organ perfusion, and an increased risk of rupture. In recent years, with the continued advancement of multi-omics sequencing technologies, the initiation and progression of AD have no longer been regarded merely as a consequence of hemodynamic injury. Instead, AD is now recognized as a complex pathological process driven by vascular smooth muscle cell (VSMC) loss, phenotypic remodeling, extracellular matrix (ECM) degradation, inflammatory amplification, and redox imbalance. Within this framework, programmed cell death (PCD) has emerged as a pivotal molecular hub linking structural destruction to intracellular dysregulation. Accumulating evidence indicates that multiple forms of PCD are involved in AD progression and interact with oxidative stress, mitochondrial dysfunction, immune cell infiltration, and matrix metalloproteinase activation to form a mutually reinforcing injury network. At present, the clinical management of AD still centers on rapid imaging-based diagnosisand timely standardized intervention, including intensive blood pressure and heart rate control, open surgical repair, and endovascular repair. Although substantial progress has been made in elucidating the mechanisms of PCD, clinical translational evidence for precision therapies targeting specific cell death pathways remains limited. Therefore, this review summarizes the mechanistic roles of PCD in AD and integrates these insights with emerging strategies for early diagnosis and precision treatment.