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Published in: Archives of Orthopaedic and Trauma Surgery 4/2003

01-05-2003 | Original Article

The angiogenic peptide vascular endothelial growth factor (VEGF) is expressed during the remodeling of free tendon grafts in sheep

Authors: Wolf Petersen, Frank Unterhauser, Thomas Pufe, Thore Zantop, Norbert P. Südkamp, Andreas Weiler

Published in: Archives of Orthopaedic and Trauma Surgery | Issue 4/2003

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Abstract

Background

Angiogenesis is important for the remodeling of autologous tendon grafts. A sheep model was used to examine the expression of the angiogenic peptide vascular endothelial growth factor (VEGF) in autologous tendon grafts after anterior cruciate ligament (ACL) reconstruction.

Methods

Merino sheep underwent ACL reconstruction with an autologous Achilles tendon split graft. VEGF and its receptors, the Fms-like tyrosine kinase receptor (FLT-1, VEGFR-1) and the kinase insert domain-containing receptor KDR (VEGFR-2/FLK-1) were detected immunohistochemically. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect which of the different VEGF splice forms are expressed during ACL remodeling.

Results

At 6 weeks, light microscopy showed zones with hypocellular necrotic graft tissue in the central part surrounded by hypercellular and hypervascularized reparative tissue invading the former graft tissue from the periphery. In contrast to the necrotic tissue, all cell types of the reparative tissue labeled strongly positive for VEGF. The VEGF receptors FLT-1 and KDR could be detected on endothelial cells of blood vessels. At 12 weeks, the complete graft diameter showed an increased vascular density (anti-factor VIII immunoreactivity), but zones of non-remodeled former graft tissue could not be found. Fusiform fibroblasts labeled strongly for VEGF. At 24 weeks, VEGF immunostaining decreased, and at 52 and 104 weeks, the grafts were largely VEGF-negative. RT-PCR supported the immunohistochemical results regarding VEGF expression and showed further that the splice variants VEGF120 and VEGF164 are expressed during angiogenesis during the remodeling of tendons.

Conclusion

We conclude that the angiogenic peptide VEGF plays a role in tendon graft remodeling.
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Metadata
Title
The angiogenic peptide vascular endothelial growth factor (VEGF) is expressed during the remodeling of free tendon grafts in sheep
Authors
Wolf Petersen
Frank Unterhauser
Thomas Pufe
Thore Zantop
Norbert P. Südkamp
Andreas Weiler
Publication date
01-05-2003
Publisher
Springer-Verlag
Published in
Archives of Orthopaedic and Trauma Surgery / Issue 4/2003
Print ISSN: 0936-8051
Electronic ISSN: 1434-3916
DOI
https://doi.org/10.1007/s00402-002-0462-z

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