Title: PlGF knockout delays brain vessel growth and maturation upon systemic hypoxic challenge
Authors: Freitas-Andrade, Moises ×
Carmeliet, Peter
Charlebois, Claudie
Stanimirovic, Danica B
Moreno, Maria J #
Issue Date: Apr-2012
Publisher: Lippincott Williams & Wilkins
Series Title: Journal of Cerebral Blood Flow and Metabolism vol:32 issue:4 pages:663-675
Article number: 10.1038/jcbfm.2011.167
Abstract: In this study, we have investigated the potential role of placental growth factor (PlGF) in hypoxia-induced brain angiogenesis. To this end, PlGF wild-type (PlGF(+/+)) and PlGF knockout (PlGF(-/-)) mice were exposed to whole body hypoxia (10% oxygen) for 7, 14, and 21 days. PlGF(+/+) animals exhibited a significant ∼40% increase in angiogenesis after 7 days of hypoxia compared with controls, while in PlGF(-/-) this effect only occurred after 14 days of hypoxia. No differences in pericyte/smooth muscle cell (SMC) coverage between the two genotypes were observed. After 14 days of hypoxia, PlGF(-/-) microvessels had a significant increase in fibrinogen accumulation and extravasation compared with those of PlGF(+/+), which correlated with endothelial cell disruption of the tight junction protein claudin-5. These vessels displayed large lumens, were surrounded by reactive astrocytes, lacked both pericyte/SMC coverage and endothelial vascular endothelial growth factor expression, and regressed after 21 days of hypoxia. Vascular endothelial growth factor expression levels were found to be significantly lower in the frontal cortex of PlGF(-/-) compared with those in PlGF(+/+) animals during the first 5 days of hypoxia, which in combination with the lack of PlGF may have contributed to the delayed angiogenic response and the prothrombotic phenotype observed in the PlGF(-/-)animals.Journal of Cerebral Blood Flow & Metabolism advance online publication, 30 November 2011; doi:10.1038/jcbfm.2011.167.
ISSN: 0271-678X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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