title: VEGF released from a fibrin biomatrix increases VEGFR-2 expression and improves early outcome after ischaemia-reperfusion injury.
abstract: Skeletal ischaemia-reperfusion (I-R) injury may influence patient outcome after severe vascular trauma or clamping of major vessels. The aim of this study was to observe whether locally applied vascular endothelial growth factor (VEGF) in fibrin could induce the expression of VEGF-receptor-2 (VEGFR-2) and improve the outcome after I-R injury. Transgenic mice expressing VEGFR-2 promoter-controlled luciferase were used for the assessment of VEGFR-2 expression. Ischaemia was induced for 2 h by a tension-controlled tourniquet to the hind limb, followed by 24 h of reperfusion. The animals were locally injected subcutaneously with fibrin sealant containing 20 or 200 ng VEGF; control animals received no treatment or fibrin sealant application. In vivo VEGFR-2 expression was quantified upon administration of luciferin at several observation times. For oedema and inflammation quantification, wet:dry ratio measurements and a myeloperoxidase assay of the muscle tissue were performed. Laser Doppler imaging showed that ischaemia was present and that the blood flow had returned to baseline levels after 24 h of reperfusion. VEGFR-2 expression levels in the fibrin + 200 ng VEGF were significantly higher than in all other groups. Granulocyte infiltration was reduced in both treatment groups, as well as reduced oedema formation. These results showed that VEGF released from fibrin had a positive effect on early I-R outcome in a mouse model, possibly via VEGFR-2. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Vienna, Austria.|Department of Trauma Surgery, Campus Innenstadt, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Moritz
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pfeifer
authors.affiliation: Department of Experimental Trauma Surgery, Klinikum Rechts der Isar, Technical University Munich, Germany.
authors.forename: Elizabeth R
authors.identifier: 0000-0002-0484-4847
authors.initials: ER
authors.lastname: Balmayor
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: Mittermayr
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wolbank
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Vienna, Austria.|Department of Experimental Trauma Surgery, Klinikum Rechts der Isar, Technical University Munich, Germany.
authors.forename: Martijn
authors.identifier: 0000-0001-5104-9881
authors.initials: M
authors.lastname: van Griensven
mesh_terms: D000818:Animals; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*
chemical_list: D015718:Fibrin Tissue Adhesive; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: fibrin sealant; ischaemia-reperfusion; vascular endothelial growth factor; vascular endothelial growth factor receptor 2