BACKGROUND: The aim of this study was to analyze the role of vascular endothelial growth factor (VEGF) binding to its high-affinity receptor kinase insert domain (KDR)-containing receptor/fetal liver kinase (flk)-1 in mediating revascularization of freely transplanted pancreatic islets in vivo. METHODS: Isolated pancreatic islets were syngeneically transplanted into dorsal skinfold chambers of Syrian hamsters. Animals were treated daily with the VEGF-KDR/flk-1 antagonist SU5416 (25 mg/kg intraperitoneally) or received vehicle for control. Intravital fluorescence microscopy and computer-assisted off-line analysis were used to study islet graft angiogenesis and revascularization during days 6, 10, and 14 after transplantation. RESULTS: In controls, islets were revascularized within 10 to 14 days after transplantation. SU5416 treatment did not affect revascularization, inasmuch as both functional capillary density and size of revascularized endocrine tissue did not differ from that of vehicle-treated controls. CONCLUSION: Because blockade of VEGF-KDR/flk-1 function does not affect islet revascularization, we conclude that VEGF signaling through its high-affinity receptor KDR/flk-1 is not an essential prerequisite for the process of new-vessel formation in freely transplanted islets of Langerhans.
BACKGROUND: The aim of this study was to analyze the role of vascular endothelial growth factor (VEGF) binding to its high-affinity receptor kinase insert domain (KDR)-containing receptor/fetal liver kinase (flk)-1 in mediating revascularization of freely transplanted pancreatic islets in vivo. METHODS: Isolated pancreatic islets were syngeneically transplanted into dorsal skinfold chambers of Syrian hamsters. Animals were treated daily with the VEGF-KDR/flk-1 antagonist SU5416 (25 mg/kg intraperitoneally) or received vehicle for control. Intravital fluorescence microscopy and computer-assisted off-line analysis were used to study islet graft angiogenesis and revascularization during days 6, 10, and 14 after transplantation. RESULTS: In controls, islets were revascularized within 10 to 14 days after transplantation. SU5416 treatment did not affect revascularization, inasmuch as both functional capillary density and size of revascularized endocrine tissue did not differ from that of vehicle-treated controls. CONCLUSION: Because blockade of VEGF-KDR/flk-1 function does not affect islet revascularization, we conclude that VEGF signaling through its high-affinity receptor KDR/flk-1 is not an essential prerequisite for the process of new-vessel formation in freely transplanted islets of Langerhans.
Authors: Maximilian M Menger; Lisa Nalbach; Leticia P Roma; Christina Körbel; Selina Wrublewsky; Matthias Glanemann; Matthias W Laschke; Michael D Menger; Emmanuel Ampofo Journal: Br J Pharmacol Date: 2020-02-10 Impact factor: 8.739