Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1alpha.

Abstract	Hypoxia-inducible factor-1alpha (HIF-1alpha) transactivates genes required for energy metabolism and tissue perfusion and is necessary for embryonic development and tumor explant growth. HIF-1alpha is overexpressed during carcinogenesis, myocardial infarction, and wound healing; however, the biological consequences of HIF-1alpha overexpression are unknown. Here, transgenic mice expressing constitutively active HIF-1alpha in epidermis displayed a 66% increase in dermal capillaries, a 13-fold elevation of total vascular endothelial growth factor (VEGF) expression, and a six- to ninefold induction of each VEGF isoform. Despite marked induction of hypervascularity, HIF-1alpha did not induce edema, inflammation, or vascular leakage, phenotypes developing in transgenic mice overexpressing VEGF cDNA in skin. Remarkably, blood vessel leakage resistance induced by HIF-1alpha overexpression was not caused by up-regulation of angiopoietin-1 or angiopoietin-2. Hypervascularity induced by HIF-1alpha could improve therapy of tissue ischemia.
Authors	D A Elson, G Thurston, L E Huang, D G Ginzinger, D M McDonald, R S Johnson, J M Arbeit
Journal	Genes & development (Genes Dev) Vol. 15 Issue 19 Pg. 2520-32 (Oct 01 2001) ISSN: 0890-9369 [Print] United States
PMID	11581158 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Angiopoietin-1 Angiopoietin-2 Angpt1 protein, mouse DNA Primers DNA, Complementary Endothelial Growth Factors Lymphokines Membrane Glycoproteins Proteins RNA, Messenger Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Ricin
Topics	Angiopoietin-1 Angiopoietin-2 Animals Base Sequence Blood Vessels (growth & development) DNA Primers DNA, Complementary Endothelial Growth Factors (genetics, metabolism) Humans Immunohistochemistry In Situ Hybridization Lymphokines (genetics, metabolism) Membrane Glycoproteins (genetics) Mice Mice, Transgenic Permeability Proteins (genetics) RNA, Messenger (genetics, metabolism) Ricin (metabolism) Skin (blood supply) Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors

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