VEGF released from a fibrin biomatrix increases VEGFR-2 expression and improves early outcome after ischaemia-reperfusion injury

Martina Moritz, Sabine Pfeifer, Elizabeth R Balmayor, Rainer Mittermayr, Susanne Wolbank, Heinz Redl, Martijn van Griensven

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)2153-2163
Number of pages11
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume11
Issue number7
DOIs
Publication statusPublished - Jul 2017
Externally publishedYes

Keywords

  • Animals
  • Fibrin Tissue Adhesive/pharmacology
  • Hindlimb/blood supply
  • Mice
  • Mice, Transgenic
  • Muscle, Skeletal/blood supply
  • Reperfusion Injury/metabolism
  • Vascular Endothelial Growth Factor A/pharmacology
  • Vascular Endothelial Growth Factor Receptor-2/biosynthesis
  • SURVIVAL
  • ISCHEMIA/REPERFUSION INJURY
  • vascular endothelial growth factor receptor 2
  • ANGIOGENESIS
  • CELL-PROLIFERATION
  • MECHANISMS
  • ischaemia-reperfusion
  • SKELETAL-MUSCLE
  • fibrin sealant
  • INHIBITION
  • INJECTION
  • vascular endothelial growth factor
  • NITRIC-OXIDE
  • ENDOTHELIAL GROWTH-FACTOR

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