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Title: Heterozygous deficiency of hypoxia-inducible factor-2alpha protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia
Authors: Brusselmans, Koenraad ×
Compernolle, Veerle
Tjwa, Marc
Wiesener, Michael S
Maxwell, Patrick H
Collen, Desire
Carmeliet, Peter #
Issue Date: May-2003
Series Title: Journal of Clinical Investigation vol:111 issue:10 pages:1519-27
Abstract: 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.
ISSN: 0021-9738
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Vesalius Research Centre (-)
Molecular and Vascular Biology
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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