DOI: 10.1161/01.res.77.3.638. Hypoxia Regulates Vascular Endothelial Growth Factor Gene Expression in Endothelial Cells

Hypoxia Regulates Vascular Endothelial Growth Factor Gene Expression in Endothelial Cells

10.1161/01.res.77.3.638

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation Research (276)

Abstract

Abstract Vascular endothelial growth factor (VEGF) is a potent mitogen specific for endothelial cells. Its expression is dramatically induced by low oxygen tension in a variety of cell types, and it has been suggested to be a key mediator of hypoxia-induced angiogenesis. Although VEGF action is targeted to endothelial cells, it is generally believed that these cells do not express VEGF. In addition, the mechanisms by which hypoxia regulates VEGF production remain unclear. We report in the present study that pulmonary artery endothelial cells do not express VEGF under basal conditions; however, significant VEGF mRNA levels accumulate when these cells are exposed to hypoxia. Using a DNA fragment containing human VEGF promoter sequence, we identified a 28-bp element that is necessary and sufficient to upregulate transcription in response to hypoxia. This element can act as a hypoxia-specific enhancer when placed upstream or downstream from a heterologous promoter. The enhancer includes, in addition to an octamer homologous to the hypoxia-inducible factor-1 (HIF-1) consensus, a sequence that resides 3′ to the consensus. Although this sequence may not be involved in the binding of HIF-1, it is absolutely required for the enhancer activity and may be the binding site for certain constitutive binding proteins. The expression of VEGF by endothelial cells in response to hypoxia may provide an important mechanism by which endothelial cell permeability and proliferation is regulated in an autocrine manner.

Bibliography

Liu, Y., Cox, S. R., Morita, T., & Kourembanas, S. (1995). Hypoxia Regulates Vascular Endothelial Growth Factor Gene Expression in Endothelial Cells. Circulation Research, 77(3), 638â643.

Authors 4

Yuxiang Liu (first)
Shanna R. Cox (additional)
Toshisuke Morita (additional)
Stella Kourembanas (additional)

References 30 Referenced 792

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Adair TH, Gay WJ, Montani JP. Growth regulation of the vascular system: evidence for a metabolic hypothesis. Am J Physiol. 1990;259:R393-R404. / Am J Physiol (1990)
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Dates

Type	When
Created	13 years, 2 months ago (June 11, 2012, 8:47 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 4:59 p.m.)
Indexed	3 days, 6 hours ago (Aug. 24, 2025, 7:05 p.m.)
Issued	29 years, 11 months ago (Sept. 1, 1995)
Published	29 years, 11 months ago (Sept. 1, 1995)
Published Print	29 years, 11 months ago (Sept. 1, 1995)

Funders 0

None

BibTeX

@article{Liu_1995, title={Hypoxia Regulates Vascular Endothelial Growth Factor Gene Expression in Endothelial Cells: Identification of a 5′ Enhancer}, volume={77}, ISSN={1524-4571}, url={http://dx.doi.org/10.1161/01.res.77.3.638}, DOI={10.1161/01.res.77.3.638}, number={3}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Liu, Yuxiang and Cox, Shanna R. and Morita, Toshisuke and Kourembanas, Stella}, year={1995}, month=sep, pages={638–643} }

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