OBJECTIVES: To identify differentially expressed proteins from the aortic tissue of thoracic aortic dissection (TAD) with hypertension and normal aorta and to explore the potential molecular pathogenesis of TAD. METHODS: Aortic tissue samples were collected from two groups of age-and gender-matched patients with TAD and normal aorta. These samples were subjected to isobaric tags for relative and absolute quantitation analysis to identify the proteins involved in TAD. Signalling pathways were analysed using the Metacore software, and the identified proteins were validated by western blotting. RESULTS: A total of 36 proteins were identified between two groups, with 19 of them being significantly down-regulated and 17 up-regulated in patients with TAD. Proteins including fibrillin-1, emilin-1, decorin, protein DJ-1 and histone H4 were validated by western blotting. The enrichment analysis performed using the Metacore process networks data showed that cell adhesion_cell-matrix interactions, proteolysis_extracellular matrix (ECM) remodelling and inflammation_interleukin 6 (IL-6) signalling were the main protein interaction networks involved in TAD. We further observed indications of increased transforming growth factor-beta (TGF-beta) signalling and impaired aortic wall remodelling, both of which may be molecular mechanisms for the pathogenesis of TAD. CONCLUSIONS: The differentially expressed proteins identified in our study are mainly involved in cell-matrix interaction, ECM remodelling and inflammation. These mechanisms, combined with the TGF-beta signalling pathway, may play an important role in the pathogenesis of TAD.