DOI: 10.1182/blood-2005-09-3541. Hypoxic induction of an HIF-1α–dependent bFGF autocrine loop drives angiogenesis in human endothelial cells

Hypoxic induction of an HIF-1α–dependent bFGF autocrine loop drives angiogenesis in human endothelial cells

10.1182/blood-2005-09-3541

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

AbstractHypoxia is a major pathophysiological condition for the induction of angiogenesis, which is a crucial aspect of growth in solid tumors. In mammalian cells, the transcriptional response to oxygen deprivation is largely mediated by hypoxia-inducible factor 1 (HIF-1), a heterodimer composed of HIF-1α and HIF-1β subunits. However, the response of endothelial cells to hypoxia and the specific involvement of HIF-α subunits in this process are still poorly understood. We show that human umbilical vein endothelial cells (HUVECs) cultured in the absence of growth factors survive and form tubelike structures when cultured under hypoxic, but not normoxic, conditions. HUVECs expressed both HIF-1α and HIF-2α when cultured under hypoxic conditions. Transfection of HIF-1α, but not HIF-2α, siRNA to HUVECs completely abrogated hypoxic induction of cords. Neutralizing antibodies to bFGF, but not IGF-1, VEGF, or PDGF-BB, blocked survival and sprouting of HUVECs under hypoxic conditions, suggesting the existence of an autocrine loop induced by low oxygen levels. Notably, bFGF-dependent induction of cord formation under normoxic conditions required HIF-1α activity, which was also essential for hypoxic induction of bFGF mRNA and protein expression. These results uncover the existence of an HIF-1α–bFGF amplification pathway that mediates survival and sprouting of endothelial cells under hypoxic conditions.

Bibliography

Calvani, M., Rapisarda, A., Uranchimeg, B., Shoemaker, R. H., & Melillo, G. (2006). Hypoxic induction of an HIF-1Î±âdependent bFGF autocrine loop drives angiogenesis in human endothelial cells. Blood, 107(7), 2705â2712.

Authors 5

Maura Calvani (first)
Annamaria Rapisarda (additional)
Badarch Uranchimeg (additional)
Robert H. Shoemaker (additional)
Giovanni Melillo (additional)

References 42 Referenced 197

Dates

Type	When
Created	19 years, 9 months ago (Nov. 22, 2005, 8:44 p.m.)
Deposited	2 years, 4 months ago (May 5, 2023, 11:23 a.m.)
Indexed	1 month ago (Aug. 3, 2025, 12:05 a.m.)
Issued	19 years, 5 months ago (April 1, 2006)
Published	19 years, 5 months ago (April 1, 2006)
Published Print	19 years, 5 months ago (April 1, 2006)

Funders 0

None

BibTeX

@article{Calvani_2006, title={Hypoxic induction of an HIF-1α–dependent bFGF autocrine loop drives angiogenesis in human endothelial cells}, volume={107}, ISSN={1528-0020}, url={http://dx.doi.org/10.1182/blood-2005-09-3541}, DOI={10.1182/blood-2005-09-3541}, number={7}, journal={Blood}, publisher={American Society of Hematology}, author={Calvani, Maura and Rapisarda, Annamaria and Uranchimeg, Badarch and Shoemaker, Robert H. and Melillo, Giovanni}, year={2006}, month=apr, pages={2705–2712} }

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