The Expression of Thrombospondin-1 in Serum and Pulmonary Arterioles of Hypoxic Pulmonary Hypertension Rats

【Abstract】 Objective To investigate the expression of thrombospondin-1 (TSP-1) in serum and pulmonary arterioles of rats with hypoxic pulmonary hypertension. Methods Twenty male Wistar rats were divided into two groups and exposed to air and isobaric hypoxia for 3 weeks respectively. The mean pulmonary artery pressure (mPAP) was measured by right cardiac catheterization. The rates of wall thickness/external diameter (WT%) and wall area/total vascular area (WA%) were calculated. The TSP-1 level in serum was measured by enzyme-linked immunosorbent assay. TSP-1 mRNA expression in lung tissue was evaluated by quantitative PCR. Results The pulmonary artery pressure increased in the hypoxia exposed rats. The chronic hypoxia also elicited the thicking of the wall and the narrowing of the lumen of pulmonary arterioles. It led to the increases of pulmonary artery pressure, the index of right ventricular hypertrophy 〔RV/(LV+S)〕, WA% and WT% compared to the controls 〔mPAP:(2.86±0.39) kPa vs. (1.35±0.28) kPa; RV/(LV+S): (43.53±3.38)% vs. (23.68±3.48)%; WT%: (35.24±11.20)% vs. (23.63±9.74)%; WA%: (55.09±12.38)% vs. (41.62±12.83)% respectively, P<0.05〕. In hypoxic group, the expression of TSP-1 mRNA in the lung was significantly up-regulated, the expression level of TSP-1 in serum was higher than that in control group （P<0.01）. Linear correlation analysis showed that TSP-1 mRNA was positively associated with WT%,WA% and mPAP （r=0.748， 0.686，0.942 respectively, P<0.05）. Conclusion The TSP-1 may play an important role in the pathogenesis process of hypoxic pulmonary vascular remodeling and pulmonary hypertension.