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

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.

Altered mTOR and Beclin-1 mediated autophagic activation during right ventricular remodeling in monocrotaline-induced pulmonary hypertension

“…Using a closed chest model, an experienced anesthesiologist isolated and cannulated the right external jugular vein using a 2 F high fidelity microtip pressure catheter under an Olympus CH30 microscope (Olympus, Tokyo, Japan). The catheter was then inserted into the superior vena cava (SVC), right atrium (RA), right ventricle, and pulmonary artery as previously described [31, 32]. Catheter position was determined in accordance with changes in the pressure waveform.…”

Identification of a Novel Gene Correlated With Vascular Smooth Muscle Cells Proliferation and Migration in Chronic Thromboembolic Pulmonary Hypertension

“…Chronic thromboembolic pulmonary hypertension is one of the most serious complications of acute pulmonary embolism ( Delcroix et al, 2013 ; Deng et al, 2016 ; Stam et al, 2018 ). Reversing the distal pulmonary artery remodeling that characterizes this condition might improve both hypoxemia and residual pulmonary hypertension (PAH) and is a goal for future CTEPH treatment ( Mandras et al, 2020 ).…”

miRNA-PDGFRB/HIF1A-lncRNA CTEPHA1 Network Plays Important Roles in the Mechanism of Chronic Thromboembolic Pulmonary Hypertension

“…As it is difficult to obtain the tissue of the human pulmonary artery, most of the studies on CTEPH are at the animal level. [19][20][21] In our previous studies, we performed the gene chip analysis of miRNA, lncRNA, and mRNA using the tissue of pulmonary arteries obtained from the CTEPH patients who underwent pulmonary endarterectomy, and the lung cancer patients who underwent pulmonary lobectomy. [14][15][16] However, the relationships between miRNA, lncRNA, and genes were not analyzed.…”