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[Role of TNF-α in vascular remodeling in rats with chronic thromboembolic pulmonary hypertension].
Chinese Journal of Tuberculosis and Respiratory Diseases 2018 August 13
Objective: To analyze the relationship between TNF-α and pulmonary vascular remodeling in order to explore the pathogenesis of CTEPH. Methods: Autologous blood clots were repeatedly injected into the left jugular vein of rats to establish the CTEPH model. Then mean pulmonary artery pressure (mPAP), histopathology, the plasma level of TNF-α, and the expressions of mRNA and protein of TNF-α in pulmonary artery were measured. Results: In the experiment group, the mPAP and vessel wall area/total area (WA/TA) ratio gradually increased as emblism extended, and increased significantly compared with the sham operation group. The plasma TNF-α concentration in the experimental group increased significantly ( P <0.05). The TNF-α proteins expressed in pulmonary artery in the 1-week, 2-week, and 4-week subgroups of experimental group increased significantly compared with the sham operation group (1.62±0.08 vs 0.85±0.12, P <0.05; 1.85±0.08 vs 0.89±0.13, P <0.05; 1.37±0.12 vs 0.91±0.15, P <0.05, respectively). Immunohistochemical results showed that TNF-α expression was higher in pulmonary artery endothelial cells of the experimental group compared with the sham operation group. The expression of pulmonary artery TNF-α protein was positively related with mPAP ( r =0.605, P <0.01), and with WA/TA ( r =0.629, P <0.01). The expression of serum TNF-α was positively related with that of pulmonary artery TNF-α protein ( r =0.721, P <0.01). Conclusion: A rat model of CTEPH can be established by repeatedly introducing autologous blood clots into the pulmonary artery with injecting TXA. Thrombosis induced higher expression of TNF-α in pulmonary arterial endothelial cells, and released into the blood. TNF-α may play an important role in the development of CTEPH, especially by contributing to vascular remodeling and PH.
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