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Abstract:

The present study was undertaken to investigate the dynamic expression of hypoxia inducible factor-1β (HIF-1β) and transforming growth factor-β 1 (TGF-β 1) in hypoxia-induced pulmonary hypertension of rats. It was found that mean pulmonary arterial pressure (mPAP) increased significantly after 7 d of hypoxia. Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d of hypoxia. HIF-1α mRNA staining was less positive in the control, hypoxia for 3 d and hypoxia for 7 d, but began to enhance significantly after 14 d of hypoxia, then remained stable. Expression of HIF-1α protein in the control was less positive, but was up-regulated in pulmonary arterial tunica intima of all hypoxic rats. TGF-β1 mRNA expression in pulmonary arterial walls was increased significantly after 14 d of hypoxia, but showed no obvious changes after 3 or 7 d of hypoxia. In pulmonary tunica adventitia and tunica media, TGF-β1 protein staining was less positive in control rats, but was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia, and then weakening after 14 and 21 d of hypoxia. Western blotting showed that HIF-1α protein levels increased significantly after 7 d of hypoxia and then remained at a high level. TGF-β1 protein level was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia, and then decreasing after 14 and 21 d of hypoxia. Linear correlation analysis showed that HIF-1α mRNA, TGF-β1 mRNA, TGF-β1 protein were positively correlated with mPAP, vessel morphometry and right ventricular hypertrophy index. TGF-β1 protein (tunica adventitia) was negatively correlated with HIF-1α mRNA. Taken together, our results suggest that changes in HIF-1α and TGF-β1 expression after hypoxia play an important role in hypoxia-induced pulmonary hypertension of rats.

Edited by Minghua XU

Keywords: hypoxia inducible factor-1α; transforming growth factor-β1; hypertension; lung; hypoxia

Document Type: Research article

DOI: 10.1111/j.1745-7270.2007.00249.x

Affiliations: 1: Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha 410001, China

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Hypoxia Induces Transforming Growth Factor-β1 Gene Expression in the Pulmonary Artery of Rats via Hypoxia-inducible Factor-1α