Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1

Dominador J. Manalo, Ashley Rowan, Tera Lavoie, Lakshmi Natarajan, Brian D. Kelly, Shui Q. Ye, Joe GN Garcia, Gregg L. Semenza

Research output: Contribution to journalArticle

725 Citations (Scopus)

Abstract

Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding angiogenic growth factors, which are secreted by hypoxic cells and stimulate endothelial cells, leading to angiogenesis. To determine whether HIF-1 also mediates cell-autonomous responses to hypoxia, we have compared gene expression profiles in arterial endothelial cells cultured under nonhypoxic versus hypoxic conditions and in nonhypoxic cells infected with adenovirus encoding beta-galactosidase versus a constitutively active form of HIF-1α (AdCA5). There were 245 gene probes that showed at least 1.5-fold increase in expression in response to hypoxia and in response to AdCA5; 325 gene probes showed at least 1.5-fold decrease in expression in response to hypoxia and in response to AdCA5. The largest category of genes down-regulated by both hypoxia and AdCA5 encoded proteins involved in cell growth/proliferation. Many genes up-regulated by both hypoxia and AdCA5 encoded cytokines/growth factors, receptors, and other signaling proteins. Transcription factors accounted for the largest group of HIF-1-regulated genes, indicating that HIF-1 controls a network of transcriptional responses to hypoxia in endothelial cells. Infection of endothelial cells with AdCA5 under nonhypoxic conditions was sufficient to induce increased basement membrane invasion and tube formation similar to the responses induced by hypoxia, indicating that HIF-1 mediates cell-autonomous activation of endothelial cells.

Original languageEnglish (US)
Pages (from-to)659-669
Number of pages11
JournalBlood
Volume105
Issue number2
DOIs
StatePublished - Jan 15 2005
Externally publishedYes

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Hypoxia-Inducible Factor 1
Endothelial cells
Endothelial Cells
Genes
Gene encoding
Growth Factor Receptors
Cell growth
Transcription
beta-Galactosidase
Gene Regulatory Networks
Angiogenesis Inducing Agents
Gene expression
Hypoxia
Transcriptome
Basement Membrane
Intercellular Signaling Peptides and Proteins
Adenoviridae
Proteins
Transcription Factors
Chemical activation

ASJC Scopus subject areas

  • Hematology

Cite this

Manalo, D. J., Rowan, A., Lavoie, T., Natarajan, L., Kelly, B. D., Ye, S. Q., ... Semenza, G. L. (2005). Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. Blood, 105(2), 659-669. https://doi.org/10.1182/blood-2004-07-2958

Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. / Manalo, Dominador J.; Rowan, Ashley; Lavoie, Tera; Natarajan, Lakshmi; Kelly, Brian D.; Ye, Shui Q.; Garcia, Joe GN; Semenza, Gregg L.

In: Blood, Vol. 105, No. 2, 15.01.2005, p. 659-669.

Research output: Contribution to journalArticle

Manalo, DJ, Rowan, A, Lavoie, T, Natarajan, L, Kelly, BD, Ye, SQ, Garcia, JGN & Semenza, GL 2005, 'Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1', Blood, vol. 105, no. 2, pp. 659-669. https://doi.org/10.1182/blood-2004-07-2958
Manalo DJ, Rowan A, Lavoie T, Natarajan L, Kelly BD, Ye SQ et al. Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. Blood. 2005 Jan 15;105(2):659-669. https://doi.org/10.1182/blood-2004-07-2958
Manalo, Dominador J. ; Rowan, Ashley ; Lavoie, Tera ; Natarajan, Lakshmi ; Kelly, Brian D. ; Ye, Shui Q. ; Garcia, Joe GN ; Semenza, Gregg L. / Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. In: Blood. 2005 ; Vol. 105, No. 2. pp. 659-669.
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