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

ABSTRACT: Hypoxia-inducible factor-2alpha (HIF-2alpha) 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-2alpha in murine endothelial cells. Surprisingly, mice with HIF-2alpha-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-2alpha-deficient ECs displayed decreased adhesion to extracellular matrix pro

SUBMITTER: Skuli N 

PROVIDER: S-EPMC2714217 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature