VEGF is important for early liver regeneration after partial hepatectomy.
BACKGROUND
The aim of the study was to determine the role of Vascular Endothelial Growth Factor (VEGF) on the microvasculature and on angiogenetic gene expression after partial hepatectomy (PH) in the rat model.


METHODS
To determine the effect of exogenous and endogenous VEGF after PH, rats were subjected to 70% PH and treated either with VEGF, anti-VEGF or NaCl. Postoperatively (3-168 h), vessel density (VD), vessel diameter (VDi), and intersinusoidal space, liver body weight ratio (LBR), hepatic proliferation and biochemical markers were assessed. To further elucidate the underlying molecular mechanisms hepatic gene expression was determined by customized cDNA arrays and quantitative RT-PCR.


RESULTS
In the VEGF group, VD, VDi, and LBR were significantly increased compared with anti-VEGF or controls. Blockage of endogenous VEGF led to a marked increase of biochemical markers. Anti-VEGF almost completely suppressed and VEGF markedly enhanced hepatic proliferation in the first 24 h after surgery. This was associated with a modulation of cell cycle control genes (PC4, Gadd45a, Tis21/BTG2), v-jun, and CD14 by VEGF.


CONCLUSIONS
VEGF plays an important role in liver regeneration and this may be due in part through its effects on neovascularization. Whether it may, when given therapeutically, represent a strategy to optimize liver regeneration in problematic patients needs to be clarified.
Bockhorn
Maximilian
M
Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, Essen, Germany. maximilian.bockhorn@uni-essen.de
Goralski
Michal
M
Prokofiev
Dennis
D
Dammann
Philipp
P
Grünewald
Petra
P
Trippler
Martin
M
Biglarnia
Alireza
A
Kamler
Markus
M
Niehues
Eva M
EM
Frilling
Andreja
A
Broelsch
Christoph E
CE
Schlaak
Jörg F
JF
D000818:Animals; D001835:Body Weight; D002455:Cell Division / Q000502:physiology; D020869:Gene Expression Profiling; D006498:Hepatectomy; D015850:Interleukin-6 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000502:physiology*
D015850:Interleukin-6; D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A