title: Vasodilator phosphostimulated protein (VASP) protects endothelial barrier function during hypoxia.
abstract: 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.
authors: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Eberhard-Karls University Tübingen, Tübingen, Germany.
authors: Marthe A
authors: MA
authors: Schmit
authors: Valbona
authors: V
authors: Mirakaj
authors: Manfred
authors: M
authors: Stangassinger
authors: Klemens
authors: K
authors: König
authors: David
authors: D
authors: Köhler
authors: Peter
authors: P
authors: Rosenberger
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