Intraluminal application of vascular endothelial growth factor enhances healing of microvascular anastomosis in a rat model

Background: Early reconstitution after injury to the endothelium is
an important feature for reducing a number of vessel wall
pathologies. We investigated the effect of vascular endothelial
growth factor ( VEGF) and its impact on the vascular remodeling
process and reendothelialization after microsurgery. Methods and
Results: Microvascular anastomosis was performed in the rat femoral
artery. One group was treated with intraluminal administration of
VEGF and the other with vehicle. We investigated morphological,
ultrastructural and immunohistochemical changes of the vascular
wall and the reendothelialization process. After 10 days,
reendothelialization was significantly faster in VEGF-treated rats.
Transmission electron microscopy revealed a complete healing in
contrast to vehicle-treated vessels. Moreover, extracellular matrix
proteins, such as fibronectin, collagen types I, III and IV, were
significantly increased. Furthermore, VEGF treatment significantly
induced VEGF receptor 2, flk-1, osteopontin and TGF-β(1) proteins.
Conclusions: Our data clearly document for the first time that
intraluminal treatment with VEGF is beneficial to the healing
process in vascular microsurgery. Osteopontin and TGF-β(1), both
induced by VEGF, may play an important role in the vascular
remodeling process. Our results provide clear evidence that VEGF
application may represent a useful strategy in accelerating
reendothelialization and improving vascular healing after
microsurgery. Copyright (C) 2005 S. Karger AG, Basel.