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Title: Survivin-dependent angiogenesis in ischemic brain: molecular mechanisms of hypoxia-induced up-regulation
Authors: Conway, Edward ×
Zwerts, Femke
Van Eygen, Veerle
DeVriese, Astrid
Nagai, Nobuo
Luo, Wei
Collen, Desire #
Issue Date: Aug-2003
Series Title: American Journal of Pathology vol:163 issue:3 pages:935-46
Abstract: Approaches to regulating angiogenesis in the brain, which may diminish parenchymal damage after stroke, are lacking. Survivin, the inhibitor of apoptosis protein, is up-regulated in vitro in vascular endothelial cells by angiogenic factors, including vascular endothelial cell growth factor (VEGF). To evaluate the in vivo role of survivin in the brain in response to hypoxia/ischemia, we used a mouse model of stroke and show that 2 days after permanent middle cerebral artery occlusion, survivin is uniquely expressed by microvessels that form in the peri-infarct and infarct regions. The extent of vascularization of the infarct is dependent on expression of survivin, since vessel density is significantly reduced in mice with heterozygous deficiency of the survivin gene (survivin+/- mice), even though infarct sizes were not different. Hypoxia alone induces survivin expression in the brain, by cultured endothelial cells and by embryonic stem cells, but this response is at least partially independent of VEGF, hypoxia inducible factor 1alpha, or placental growth factor. Delineating the spatiotemporal pattern of expression of survivin after stroke, and the molecular mechanisms by which this is regulated, may provide novel approaches to therapeutically optimize angiogenesis in a variety of ischemic disorders.
URI: 
ISSN: 0002-9440
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Vesalius Research Centre (-)
× corresponding author
# (joint) last author

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