The role of tissue factor and autophagy in pulmonary vascular remodeling in a rat model for chronic thromboembolic pulmonary hypertension.

Chaosheng Deng,Haibo Ding,Zhanghua Zhong,Ningfang Lian,Kaixiong Liu,Yunfei Chen,Dawen Wu,Qiaoxian Zhang,Minxia Yang,Shuang Wu

doi:10.1186/s12931-016-0383-y

Abstract

BackgroundFew reports have examined tissue factor (TF) and autophagy expression in chronic pulmonary thromboembolic hypertension (CTEPH) animal models. Objectives: To investigate the role of tissue factor (TF), autophagy and their interactions during chronic thromboembolic pulmonary hypertension (CTEPH) pathogenesis in a rat model.MethodsAutologous blood clots were repeatedly injected into the left jugular vein of rats with injecting endogenous fibrinolysis inhibitor tranexamic acid (TXA). Mean pulmonary arterial pressure (mPAP), histopathology and TF, Beclin-1 and microtubule-associated protein 1 light chain (LC3) expression levels were detected.ResultsThe mPAP and vessel wall area/total area (WA/TA) ratio in the experiment group increased significantly (P < 0.05). TF mRNA and protein expression levels in the experiment group increased significantly (P < 0.05). Beclin-1 and LC3B mRNA and protein expression levels were lower in the experiment group (P < 0.05). The mPAP had a positive correlation with WA/TA ratio (r = 0.955, P < 0.05). Beclin-1 and LC3B protein expression had a negative correlation with the WA/TA ratio (r = -0.963, P < 0.05, r = -0.965, P < 0.05, respectively). TF protein expression had a negative correlation with both Beclin-1 and LC3B protein expression (r = -0.995, P <0.05, r = -0972, P < 0.05, respectively).ConclusionsA rat model of CTEPH can be established by repeatedly introducing autologous blood clots into the pulmonary artery with injecting TXA. TF and autophagy may play a key role during CTEPH pathogenesis, especially in vascular remodeling.

Highlights

Few reports have examined tissue factor (TF) and autophagy expression in chronic pulmonary thromboembolic hypertension (CTEPH) animal models
46.67 ± 8.50a 49.06 ± 8.82ad 54.03 ± 10.26ac Mean pulmonary arterial pressure (mPAP) mean pulmonary arterial pressure, WA/TA Vessel wall area/total area aindicated that mPAP and WA/TA in the experimental group compared to sham operation group (P < 0.05, respectively) in the 1, 2, and 4-week subgroups. bindicated that the mPAP in the 4-week subgroup compared to 1-week subgroup (P 0.05) in the experimental group. cindicated that the WA/TA in the 4-week subgroup compared to 1-week subgroup (P >0.05) and 2-week subgroup (P >0.05) in the experimental group. dindicated that the mPAP and WA/TA in the 2-week subgroup compared to
The pulmonary artery endothelial cells were closely connected with the thrombus (Fig. 2e) in the thromboembolic pulmonary artery and a thickened intima was apparent in the distal pulmonary artery (Fig. 2f)

Summary

Introduction

Few reports have examined tissue factor (TF) and autophagy expression in chronic pulmonary thromboembolic hypertension (CTEPH) animal models. Objectives: To investigate the role of tissue factor (TF), autophagy and their interactions during chronic thromboembolic pulmonary hypertension (CTEPH) pathogenesis in a rat model. The most common pulmonary embolus is thrombus, known as pulmonary thromboembolism (PTE). Few reports have examined CTEPH animal models because of their robust fibrinolytic system. We have successfully established a chronic PTE animal model for the study of lung ischemia reperfusion injury using tranexamic acid (TXA) that inhibits endogenous fibrinolysis [4]. Since large animals such as dogs are more expensive and prohibitive in terms of large-scale experiments, we have successfully established a rat model of CTEPH

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