Long Noncoding RNAs in Aortic Dissection: Mechanistic Roles and Therapeutic Potential

Aortic dissection (AD) is a life-threatening vascular disorder characterized by separation of the layers of the aortic wall, primarily triggered by an intimal tear or an intramural hemorrhage. Age is a well-recognized and critical risk factor for AD. Epidemiological evidence consistently demonstrates a strong positive correlation between age and AD incidence, with peak occurrence in the 50-70-year age group. Its pathogenesis involves vascular inflammation, extracellular matrix (ECM) degradation, vascular smooth muscle cell (VSMC) phenotypic switching, apoptosis, and immune cell infiltration. Two major pathophysiological theories have been proposed: one suggests a primary intimal tear, and the other involves medial degeneration from stress concentration. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides and account for ~80% of the human noncoding transcriptome. They exert diverse biological functions (e.g., miRNA sponging, protein scaffolding, transcriptional regulation) and are pivotal in diseases such as cancer, rheumatoid arthritis, and AD. Despite emerging evidence linking lncRNAs to AD, most studies to date have focused only on their role as competing endogenous RNAs (ceRNAs), with limited mechanistic depth and scarce clinical validation. This review summarizes the pathophysiology of AD and systematically discusses lncRNA-mediated mechanisms in AD progression. We highlight current knowledge gaps and propose future directions for exploring lncRNAs as potential therapeutic targets to improve AD prognosis.