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.


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-beta(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-beta(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.
Infanger
Manfred
M
Department of Trauma and Reconstructive Surgery, Charité-University Medicine Berlin, Benjamin Franklin Campus, Hindenburgdamm 30, DE-12200 Berlin, Germany.
Shakibaei
Mehdi
M
Kossmehl
Peter
P
Hollenberg
Siri M
SM
Grosse
Jirka
J
Faramarzi
Shideh
S
Schulze-Tanzil
Gundula
G
Paul
Martin
M
Grimm
Daniela
D
D000287:Administration, Topical; D000714:Anastomosis, Surgical; D000818:Animals; D003094:Collagen / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005263:Femoral Artery / Q000503:physiopathology* / Q000601:surgery* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008866:Microsurgery; D053495:Osteopontin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000378:metabolism; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014654:Vascular Patency; D014945:Wound Healing / Q000187:drug effects*
D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D053495:Osteopontin; D003094:Collagen; D040301:Vascular Endothelial Growth Factor Receptor-2