Endothelial deletion of hypoxia-inducible factor-2α (HIF-2α) alters vascular function and tumor angiogenesis

Nicolas Skuli, Liping Liu, Anja Runge, Tao Wang, Lijun Yuan, Sunny Patel, Luisa Iruela-Arispe, M. Celeste Simon, Brian Keith

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

Hypoxia-inducible factor-2α (HIF-2α) 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-2α in murine endothelial cells. Surprisingly, mice with HIF-2α-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-2α-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-2α in vascular endothelial cells.

Original languageEnglish (US)
Pages (from-to)469-477
Number of pages9
JournalBlood
Volume114
Issue number2
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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