Journal
INFLAMMATION
Volume 35, Issue 2, Pages 566-573Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-011-9347-z
Keywords
vasodilator-stimulated phosphoprotein; barrier function; endothel; hypoxia
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Funding
- Fonds National de la Recherche (FNR)
- Deutsche Forschungsgemeinschaft (DFG) [DFG-RO 3671/4-1]
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The endothelial barrier controls the passage of solutes from the vascular space. This is achieved through active reorganization of the actin cytoskeleton. A central cytoskeletal protein involved into this is vasodilator-stimulated phosphoprotein (VASP). However, the functional role of endothelial VASP during hypoxia has not been thoroughly elucidated. We determined endothelial VASP expression through real-time PCR (Rt-PCR), immunhistochemistry, and Western blot analysis during hypoxia. VASP promoter studies were performed using a PGL3 firefly luciferase containing plasmid. Following approval by the local authorities, VASP(-/-) mice and littermate controls were subjected to normobaric hypoxia (8% O-2, 92% N-2) after intravenous injection of Evans blue dye. In in vitro studies, we found significant VASP repression in human microvascular and human umbilical vein endothelial cells through Rt-PCR, immunhistochemistry, and Western blot analysis. The VASP promoter construct demonstrated significant repression in response to hypoxia, which was abolished when the binding of hypoxia-inducible factor 1 alpha was excluded. Exposure of wild-type (WT) and VASP(-/-) animals to normobaric hypoxia for 4 h resulted in an increase in Evans blue tissue extravasation that was significantly increased in VASP(-/-) animals compared to WT controls. In summary, we demonstrate here that endothelial VASP holds significant importance for endothelial barrier properties during hypoxia.
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