[Role of TNF-α in vascular remodeling in rats with chronic thromboembolic pulmonary hypertension].

To analyze the relationship between TNF-α and pulmonary vascular remodeling in order to explore the pathogenesis of CTEPH. 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. 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 (<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 0.85±0.12, <0.05; 1.85±0.08 0.89±0.13, <0.05; 1.37±0.12 0.91±0.15, <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 (=0.605, <0.01), and with WA/TA (=0.629, <0.01). The expression of serum TNF-α was positively related with that of pulmonary artery TNF-α protein (=0.721, <0.01). 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.