Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia

Hugo J.H. Marti, Myriam Bernaudin, Anita Bellail, Heike Schoch, Monika Euler, Edwige Petit, Werner Risau

Research output: Contribution to journalArticle

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Abstract

We investigated the hypothesis that hypoxia induces angiogenesis and thereby may counteract the detrimental neurological effects associated with stroke. Forty-eight to seventy-two hours after permanent middle cerebral artery occlusion we found a strong increase in the number of newly formed vessels at the border of the infarction. Using the hypoxia marker nitroimidazole EF5, we detected hypoxic cells in the ischemic border of the neocortex. Expression of vascular endothelial growth factor (VEGF), which is the main regulator of angiogenesis and is inducible by hypoxia, was strongly up-regulated in the ischemic border, at times between 6 and 24 hours after occlusion. In addition, both VEGF receptors (VEGFRs) were up-regulated at the border after 48 hours and later in the ischemic core. Finally, the two transcription factors, hypoxia-inducible factor-1 (HIF-1) and HIF-2, known to be involved in the regulation of VEGF and VEGFR gene expression, were increased in the ischemic border after 72 hours, suggesting a regulatory function for these factors. These results strongly suggest that the VEGF/VEGFR system, induced by hypoxia, leads to the growth of new vessels after cerebral ischemia. Exogenous support of this natural protective mechanism might lead to enhanced survival after stroke.

Original languageEnglish (US)
Pages (from-to)965-976
Number of pages12
JournalAmerican Journal of Pathology
Volume156
Issue number3
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor
Brain Ischemia
Vascular Endothelial Growth Factor A
Stroke
Nitroimidazoles
Hypoxia-Inducible Factor 1
Middle Cerebral Artery Infarction
Neocortex
Infarction
Transcription Factors
Hypoxia
Gene Expression
Growth

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. / Marti, Hugo J.H.; Bernaudin, Myriam; Bellail, Anita; Schoch, Heike; Euler, Monika; Petit, Edwige; Risau, Werner.

In: American Journal of Pathology, Vol. 156, No. 3, 01.01.2000, p. 965-976.

Research output: Contribution to journalArticle

Marti, Hugo J.H. ; Bernaudin, Myriam ; Bellail, Anita ; Schoch, Heike ; Euler, Monika ; Petit, Edwige ; Risau, Werner. / Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. In: American Journal of Pathology. 2000 ; Vol. 156, No. 3. pp. 965-976.
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