Journal
BLOOD
Volume 114, Issue 2, Pages 469-477Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-12-193581
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Funding
- Howard Hughes Medical Institute
- National Institutes of Health [HL66130]
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Hypoxia-inducible factor-2 alpha (HIF-2 alpha) is highly expressed in embryonic vascular endothelial cells (ECs) and activates the expression of target genes whose products modulate vascular function and angiogenesis. In this report, we describe a genetic model designed to test the physiologic consequences of deleting HIF-2 alpha in murine endothelial cells. Surprisingly, mice with HIF-2 alpha-deficient ECs developed normally but displayed a variety of phenotypes, including increased vessel permeability, aberrant endothelial cell ultrastructure, and pulmonary hypertension. Moreover, these animals exhibited defective tumor angiogenesis associated with increased hypoxic stress and tumor cell apoptosis. Immortalized HIF-2 alpha-deficient ECs displayed decreased adhesion to extracellular matrix proteins and expressed reduced levels of transcripts encoding fibronectin, integrins, endothelin B receptor, angiopoietin 2, and delta-like ligand 4 (Dll4). Together, these data identify unique cell-autonomous functions for HIF-2 alpha in vascular endothelial cells. (Blood. 2009; 114: 469-477)
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