The role of β-catenin in pulmonary artery endothelial-mesenchymal transformation in rats with chronic thromboembolic pulmonary hypertension.

Abstract

β-catenin and endothelial mesenchymal transformation play an important role in the formation of pulmonary hypertension. To explore the role of β-catenin in chronic thromboembolic pulmonary hypertension (CTEPH), we first established a rat model of CTEPH by repeated autologous thromboembolization and then treated these rats with a β-catenin specific inhibitor, XAV939, for two or four weeks. We further examined the expression of β-catenin, α-SMA and CD31, mean pulmonary artery pressure (mPAP), and histopathology in the pulmonary artery, and analyzed their correlation. In the thrombus group without treatment of the inhibitor, the expression of β-catenin and α-SMA in pulmonary artery was increased with time; mPAP, the thickness of pulmonary artery wall, and the area/total area of pulmonary artery (WA/TA) were also increased; however, the expression of CD31 was decreased. Interestingly, these symptoms could be improved by treatment with XAV939. In this study, in CTEPH rat model, the expression of β-catenin signal affects pulmonary vascular remodeling and pulmonary artery pressure, and positively correlated with pulmonary arterial endothelial mesenchymal transformation (EMT), indicating that β-catenin signal may play an important role in the occurrence and development of CTEPH. The inhibition of β-catenin signal and the improvement of pulmonary arterial EMT may provide therapeutic ideas for CTEPH.