The effects of HIF and VEGF on pulmonary hypertension induced by chronic hypoxic hypercapnia

Objective:To explore the expression of Hypoxia-inducible factor 1α(HIF-1α)pro-tein and vascular endothelial growth factor(VEGF) protein in mice with pulmonary hypertension induced by chronic hypoxic hypercapnia, and investigate whether HIF signal path to regulate the expression of VEGF. Methods: Sixteen male C57bl/6 mice were randomly divided into two groups: the control group (group C) and the group with hypoxic hypercapnia for 4 weeks (group H). The right ventricular systolic pressure (RVSP) and the ratio of RV/(LV+S)) were measured. Lung sections were stained with hematoxylin and eosin (HE) for morphologic studies under light microscope. The expression of HIF-1αprotein and VEGF protein of pulmonary arterioles was also observed with immunohistochemistry. Results: ①The values of the RVSP, RV/LV+S in group H were significantly higher than that in group C. ②The vessel walls of the pulmonary arterioles of group H were thicken, the smooth muscle cells in tunica media were proliferated and the lumens of the pulmonary arterioles were narrowed under light microscope. ③Both HIF-1αprotein and VEGF protein staining were positive in the lung of pulmonary arterioles of group H with immunohistochemistry. The average optical density of HIF-1αand VEGF protein with immunohistochemistry in the pulmonary arterioles in group H was significantly higher than that in group C. There was positive correlation between VEGF protein and HIF-1α protein. Conclusion: HIF-1αprotein and VEGF protein are induced to express by chronic hypoxic, and involved in the pathogenesis with pulmonary hypertension in mice.