The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Heterozygous deficiency of hypoxia-inducible factor–2α protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia
Open accessAbstract
Chronic hypoxia induces pulmonary vascular remodeling, leading to pulmonary hypertension, right ventricular hypertrophy, and heart failure. Heterozygous deficiency of hypoxia-inducible factor-1alpha (HIF-1alpha), which mediates the cellular response to hypoxia by increasing expression of genes involved in erythropoiesis and angiogenesis, has been previously shown to delay hypoxia-induced pulmonary hypertension. HIF-2alpha is a homologue of HIF-1alpha and is abundantly expressed in the lung, but its role in pulmonary hypertension remains unknown. Therefore, we analyzed the pulmonary response of WT and viable heterozygous HIF-2alpha-deficient (Hif2alpha(+/-)) mice after exposure to 10% O(2) for 4 weeks. In contrast to WT mice, Hif2alpha(+/-) mice were fully protected against pulmonary hypertension and right ventricular hypertrophy, unveiling a critical role of HIF-2alpha in hypoxia-induced pulmonary vascular remodeling. Pulmonary expression levels of endothelin-1 and plasma catecholamine levels were increased threefold and 12-fold respectively in WT but not in Hif2alpha(+/-) mice after hypoxia, suggesting that HIF-2alpha-mediated upregulation of these vasoconstrictors contributes to the development of hypoxic pulmonary vascular remodeling.
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Cites
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“known HIF-1α target gene (16), are increased in patients with pulmonary hypertension (4, 7), and inhibition of ET-1 or its receptor prevents hypoxiainduced pulmonary hypertension and vascular remodeling (4).”
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Cited by
Hypoxia-inducible factors in physiology and medicine
Semenza, G. L. (2012) · Cell · doi:10.1016/j.cell.2012.01.021 · Cited by 3,645
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Regulation of Oxygen Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (2009) · Physiology · doi:10.1152/physiol.00045.2008 · Cited by 926
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Hypoxia signaling in human health and diseases: implications and prospects for therapeutics
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Metadata
- Authors
- Brusselmans, K., Compernolle, V., Tjwa, M., Wiesener, M. S., Maxwell, P. H., Collen, D., & Carmeliet, P.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-05-15
- Volume
- 111
- Issue
- 10
- Pages
- 1519-1527
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2131676053
- Cited by
- 316
- References
- 37
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- bronze
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