A proteomic study of the aortic media in human thoracic aortic dissection: Implication for oxidative stress

Objective: The aortic media lesion is a key pathologic feature in thoracic aortic dissection. To identify key proteins in aortic media lesions that may contribute to its pathogenesis, we performed proteomic studies to find differentially expressed proteins in the media from diseased and normal thoracic aorta. Methods: Ascending aortic segments were obtained from patients with thoracic aortic dissection (n = 8) and age-matched normal donors ( n 5 6). The differentially expressed proteins of their media tissues were analyzed by 2-dimensional electrophoresis and mass spectrometry, and verified by Western blotting. Oxidative stress was measured by functional assays in a larger sample size (15 patients and 10 controls). Results: Image analysis of the protein profiles from 2-dimensional gels revealed 126 differentially expressed proteins, of which 26 were identified by mass spectrometry. Among them, extracellular superoxide dismutase, an enzyme involved in oxidative stress, was selected for further studies. Western blotting showed that extracellular superoxide dismutase expression was more than 50% lower in patient samples than in controls (P < .001). Superoxide dismutase activity was consistently decreased (P <.001) and lipid peroxidation was increased (P = .019) in patient media homogenates compared with that in controls. Conclusion: Our results indicate that protein expression profiles in the aortic media from thoracic aortic dissection differ significantly from that of controls, which may provide important insights into the disease mechanisms. This study also suggests that increased oxidative stress may play an important role in the disease.