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Gene expression analysis in control and HIF-2 alpha deficient murine lung endothelial cells under hypoxia


ABSTRACT: Journal : Blood. 2009 Jul 9;114(2):469-77. Epub 2009 May 13. Title : Endothelial deletion of hypoxia-inducible factor-2alpha (HIF-2alpha) alters vascular function and tumor angiogenesis. Authors : Skuli N, Liu L, Runge A, Wang T, Yuan L, Patel S, Iruela-Arispe L, Simon MC, Keith B. 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 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-2alpha in vascular endothelial cells. Keywords: Murine lung endothelial cell study Cnt1,2 and 3 (Hif-2a floxed/floxed) cells were subjected to 0.5% oxygen treatment for 16hrs and KO1,2 and 3 (Hif-2a knockout) cells were subjected to 0.5% oxygen treatment for 16hrs.

ORGANISM(S): Mus musculus

SUBMITTER: Nicolas Skuli 

PROVIDER: E-GEOD-16067 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Skuli Nicolas N   Liu Liping L   Runge Anja A   Wang Tao T   Yuan Lijun L   Patel Sunny S   Iruela-Arispe Luisa L   Simon M Celeste MC   Keith Brian B  

Blood 20090513 2


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 permeabi  ...[more]

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