Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension
Q Li, A Dai - Chinese medical journal, 2004 - mednexus.org
Q Li, A Dai
Chinese medical journal, 2004•mednexus.orgBackground Hypoxia-inducible factor-1α (HIF-1α) is one of the pivotal mediators in the
response of lungs to decreased oxygen availability, and increasingly has been implicated in
the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a
downstream target gene of HIF-1α, plays an important role in the pathogenesis of hypoxic
pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we
investigated the dynamic expression of HIF-1α and VEGF in pulmonary artery of rats with …
response of lungs to decreased oxygen availability, and increasingly has been implicated in
the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a
downstream target gene of HIF-1α, plays an important role in the pathogenesis of hypoxic
pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we
investigated the dynamic expression of HIF-1α and VEGF in pulmonary artery of rats with …
Background
Hypoxia-inducible factor-1α (HIF-1α) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a downstream target gene of HIF-1α, plays an important role in the pathogenesis of hypoxic pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we investigated the dynamic expression of HIF-1α and VEGF in pulmonary artery of rats with hypoxia-induced pulmonary hypertension.
Methods
Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were estimated. Lungs were inflated and fixed for in situ hybridisation and immunohistochemistry.
Results
mPAP values were significantly higher than the control values after 7days of hypoxia [(18. 4 ± 0. 4) mmHg, P <0. 05]. RVHI developed significantly after 14 days of hypoxia. Expression of HIF-1α protein increased in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, HIF-1α protein was markedly increased by day 3 (0. 20 ± 0. 02, P<0. 05), reached the peak by day 7, then declined after day 14 of hypoxia. HIF-1α mRNA increased significantly after day 14 of hypoxia (0. 20 ± 0. 02, P<0. 05). VEGF protein began to increase markedly after day 7 of hypoxia, reaching its peak around day 14 of hypoxia (0. 15±0. 02, P<0. 05). VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and tunica media, whereas VEGF protein is located predominantly in tunica intima. Linear analysis showed that HIF-1α mRNA, VEGF and mPAP were correlated with hypoxic pulmonary artery remodelling. HIF-1α mRNA was positively correlated with VEGF mRNA and protein (P<0. 01).
Conclusion
HIF-1α and VEGF are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rats. Chin Med J 2004; 117(7):1023-1028
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