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

Respir Res. 2016 May 27;17(1):65. doi: 10.1186/s12931-016-0383-y.

Abstract

Background: 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.

Methods: Autologous 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.

Results: The 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).

Conclusions: A 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifibrinolytic Agents / pharmacology
  • Arterial Pressure
  • Autophagy*
  • Beclin-1 / biosynthesis
  • Beclin-1 / genetics
  • Hypertension, Pulmonary / genetics
  • Hypertension, Pulmonary / physiopathology*
  • Male
  • Microtubule-Associated Proteins / biosynthesis
  • Microtubule-Associated Proteins / genetics
  • Pulmonary Artery / pathology
  • Pulmonary Artery / physiopathology
  • Pulmonary Circulation*
  • Pulmonary Embolism / genetics
  • Pulmonary Embolism / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Thromboplastin / genetics*
  • Tranexamic Acid / pharmacology
  • Vascular Remodeling*

Substances

  • Antifibrinolytic Agents
  • Beclin-1
  • LC3 protein, rat
  • Microtubule-Associated Proteins
  • Tranexamic Acid
  • Thromboplastin