Role of FoxO1 in pulmonary artery endothelial autophagic function in chronic thromboembolic pulmonary hypertension rats

Abstract

Abstract Aims To detect the effect of forkhead box transcription factor O-1 (FoxO1) on autophagy of pulmonary artery in chronic thromboembolic pulmonary hypertension (CTEPH) rats. Methods Rats were divided into sham group and three experimental groups. In the experimental group, autologous blood clots were injected into the right jugular vein of rats to induce the CTEPH animal model. The experimental group was randomly divided into three groups, thrombosis group (n = 24), FoxO1 agonist treatment group (resveratrol) (n = 24) and FoxO1 inhibitor treatment group (AS1842856) group (n = 24). The mean pulmonary arterial pressure (mPAP), the area of pulmonary artery wall/total area (WA/TA) and the expression levels of FoxO1, pFoxO1, LC3 and Beclin1 in pulmonary artery were measured. Results The mPAP and WA/TA ratio in the FoxO1 agonist group were decreased significantly (P < 0.05). The mPAP and WA/TA ratio in the FoxO1 inhibitor were increased significantly (P < 0.05). The mPAP was negatively correlated with pFoxO1 in experimental group (r=-0.967, P < 0.001), the expression of pFoxO1 protein was positively correlated with FoxO1 protein expression (r = 0.972, P < 0.001), expression of LC3 protein was positively correlated with the expression of pFoxO1 protein (r = 0.871, P < 0.001), Beclin1 protein expression was positively correlated with pFoxO1 protein expression (r = 0.953, P < 0.001). Conclusion There is a decreased autophagy activity and FoxO1 expression of pulmonary artery in CTEPH rats. FoxO1 may be involved in pulmonary artery remodeling process and contribute to the development of CTEPH by regulating autophagy activity, but the concrete mechanism are unknown.