Expression of tissue factor and forkhead box transcription factor O-1 in a rat model for chronic thromboembolic pulmonary hypertension.

Abstract

Few reports have examined tissue factor (TF) and forkhead box transcription factor O-1 (FoxO1) expression in chronic thromboembolic pulmonary hypertension (CTEPH) animal models. To investigate the role of TF and FoxO1 and their interactions during CTEPH pathogenesis in a rat model. Autologous blood clots were repeatedly injected into the pulmonary arteries through right jugular vein to induce a rat model of CTEPH. Hemodynamic parameters, histopathology, and TF and FoxO1expression levels were detected. The mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance and vessel wall area/total area (WA/TA) ratio in the experiment group increased significantly than sham group (P<0.05). The cardiac output in the 1-, 2-, and 4-week groups decreased significantly (P<0.05) when compared to sham group. TF mRNA expression levels in the experiment group increased significantly than sham group (P<0.05). FoxO1 mRNA and protein expression levels were lower in the experiment group than sham group (P<0.05). The mPAP had a positive correlation with WA/TA ratio (r=0.45, P=0.01). TF mRNA expression had a positive correlation with WA/TA ratio (r=0.374, P=0.035) and a positive correlation with mPAP (r=0.48, P=0.005). FoxO1 mRNA expression had a negative correlation trend with the WA/TA ratio (r=-0.297, P=0.099) and a negative correlation trend with mPAP (r=-0.34, P=0.057). TF mRNA expression had a negative correlation with FoxO1 mRNA expression (r=-0.62, P<0.001). A rat model of CTEPH can be successfully established by the injection of autologous blood clots into the pulmonary artery. TF and FoxO1 may play a key role in vascular remodeling during CTEPH pathogenesis.