Disturbed P53-MDM2 feedback loop contributes to thoracic aortic dissection formation and may be a result of TRIM-25 overexpression.

The development of thoracic aortic dissection (TAD) is attributed to a broad range of degenerative, genetic, structural, oxidative, apoptotic, and acquired disease states. In this study, we examined the role of the disturbed p53-MDM2 feed-back loop in the formation of TAD, and one of a potential feed-back loop regulator, TRIM-25.,Surgical specimens of the aorta from TAD patients (n=10) and controls (n=10) were tested for α-smooth muscle actin (α-SMA),p53,murine double minute2(MDM2) and tripartite motif protein-25(TRIM-25) by western blot, immunohistochemical staining and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) , respectively.,When compared with controls, western blot shows that the protein levels of p53,MDM2 and TRIM25 was increased significantly in the aortic media of thoracic aortic dissection patients. qRT-PCR further verified the mRNA expression of MDM2 and TRIM25 were also increased 6 and 4 folds respectively in the TAD media of the aortic wall. Immunohistochemistry results showed significantly decreased staining of α-SMA,smoth muscle cells and more collagen deposition in the media of the aortic wall from patients with TAD.,This study provided a new insight into the disturbed p53-MDM2 feedback loop in the pathogenesis of TAD, and this may be because of the TRIM25 overexpression.