The roles of hypoxia-inducible factor-1 alpha and vascular endothelial growth factor in the pathogenesis of hypoxia-induced pulmonary hypertension in neonatal rats

Abstract

Objective To study the roles of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH) in neonatal rats. Methods Wistar neonatal rats were assigned into HPH group and the control group using random number table method.Neonatal rats in HPH group were exposed to hypoxia according to HPH model.On day 3, 7, 14 and 21 of hypoxia, the mean pulmonary artery pressure (mPAP), the level of mRNA and protein expression of HIF-1α and VEGF in lung tissue were examined using RT-PCR and Western blot methods respectively.The correlation of HIF-1α, VEGF and mPAP were also analyzed. Results The mPAP (mmHg) in HPH group on day 3, 7, 14 and 21 of hypoxia were all higher than the control group[(8.5±1.5)vs.(5.2±1.0), (12.1±2.1)vs.(9.6±0.8), (12.9±2.0)vs.(9.1±0.8), (21.0±2.3)vs.(11.2±1.6), P< 0.05]. On day 3, 7 and 14 of hypoxia, the mRNA of HIF-1α in lung tissue of HPH group were significantly higher than the control group(P< 0.05). On day 7 of hypoxia, the HIF-1α protein in lung tissue of HPH group was significantly higher than the control group(P< 0.05). On day 7, 14 and 21 of hypoxia, the mRNA and protein of VEGF in lung tissue of HPH group were also significantly higher than the control group(P< 0.05). Correlation analysis showed that HIF-1α protein were positively correlated with mPAP on day 3, 7, 14 and 21 of hypoxia in HPH group(r=0.504, P=0.002), and VEGF protein were positively correlated with mPAP in HPH group on day 7, 14 and 21 of hypoxia(r=0.782, P<0.001). Conclusion Both HIF-1α and VEGF play roles in the occurrence and development of HPH in neonatal rats. Key words: Hypertension, pulmonary; Hypoxia-inducible factor 1, alpha subunit; Vascular endothelial growth factors; Rats