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Expression and role of factor inhibiting hypoxia-inducible factor-1 in pulmonary arteries of rat with hypoxia-induced hypertension

Expression and role of factor inhibiting hypoxia-inducible f...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Dai-Yan FU,Ai-Guo DAI,Rui-Cheng HU,Yun-Chong CHEN,Li-Ming ZHU Department of Respiratory Medicine,Hunan Institute of Gerontology,Hunan Province Geriatric Hospital,Changsha 410016,China

＜正＞Hypoxia-inducible factor-1（HIF-1） plays a pivotal role during the development of hypoxia-induced pulmonary hypertension（HPH） through transactiviating target *** inhibiting HIF-1（FIH）,as an oxygen-sensitive attenuator,hydroxylates a conserved asparagines residue within the C-terminal transactivation domain（CTAD） of HIF-1αunder normoxia and moderate *** protein is down-regulated in response to *** dynamic expression and role of FIH during the development of HPH remain *** investigate this,a HPH rat model was *** pulmonary arterial pressure（mPAP） increased significantly after 7d of hypoxia. Pulmonary artery remodeling index became evident after 7 d of hypoxia,while right ventricular hypertrophy became significant after 14 d of *** mRNA and protein expression of HIF-1 and VEGF,a well-characterized target gene of HIF-1αwere markedly up-regulated after exposure to hypoxia in tunica intima and tunica media of pulmonary *** protein,in pulmonary arterial walls,declined after 7 d of hypoxia and lessened further as the duration of hypoxia *** mRNA had little changes after exposure to hypoxia compared with normoxia. In hypoxic rats,HIF-1αmRNA,HIF-1αprotein,VEGF mRNA and VEGF protein were positively correlated with mPAP,pulmonary artery remodeling index and *** protein showed significant negative correlations with VEGF mRNA and VEGF *** protein was negatively correlated with mPAP,pulmonary artery remodeling index and *** together,our results suggest that in the pulmonary arteries of rat exposed to moderate hypoxia,a time-dependent decrease in FIH protein may contribute to development of rat HPH through enhancing the transactivation of HIF-1αtarget genes such as VEGF.

关键词： hypoxia-inducible factor-1 factor inhibiting hypoxia-inducible factor-1 asparaginl hydroxylase hypertension pulmonary

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