Blockade of in vivo VEGF-KDR/flk-1 signaling does not affect revascularization of freely transplanted pancreatic islets.
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.


CONCLUSIONS
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.
Schramm
Rene
R
Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
Yamauchi
Jun-Ichiro
J
Vollmar
Brigitte
B
Vajkoczy
Peter
P
Menger
Michael D
MD
D000818:Animals; D006224:Cricetinae; D016228:Endothelial Growth Factors / Q000502:physiology; D007211:Indoles / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D007515:Islets of Langerhans / Q000098:blood supply*; D016381:Islets of Langerhans Transplantation; D008222:Lymphokines / Q000502:physiology; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D007211:Indoles; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C116890:Semaxinib; D040301:Vascular Endothelial Growth Factor Receptor-2