VEGF-A and -C but not -B mediate increased vascular permeability in preserved lung grafts.
BACKGROUND
Vascular endothelial growth factor (VEGF) is a potent endothelial cell growth and permeability factor, expressed in the lung. Overexpression of VEGF is associated with increased vascular permeability in the early stage of acute lung injury in mice. The role of various forms of VEGF in transplantation-induced lung injury is not well understood.


METHODS
VEGF mRNA and protein expression was measured in biopsies of preserved donor lung grafts as well as in control lung biopsies, using real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. VEGF tissue expression was also evaluated by immunocytochemistry. Serum VEGF was measured in recipients after transplantation and in controls using ELISA.


RESULTS
Although VEGF-A and VEGF-C protein expression was up-regulated, their mRNA levels were decreased in donor versus control lung biopsies (P<0.05). VEGF-B mRNA was decreased, but its protein level was unchanged in donors. Flt-1 was unchanged, KDR gene expression was down-regulated in donors (P<0.05), and both receptors' protein expression was under the detection level in donor and control lungs. VEGF-A was detected in pulmonary vessels and bronchi, whereas VEGF-C was only detectable in vessels of both donor and control lungs. After transplantation, serum VEGF increased (P<0.05) and returned to control baseline levels 12 weeks after surgery. Wet-to-dry lung weight was increased in donor versus control lungs.


CONCLUSIONS
These results indicate that unventilated hypoxia increases vascular permeability in lung grafts and that this process is mainly regulated at VEGF-A and VEGF-C translational but not transcriptional level. Selective VEGF antagonism during graft preservation might be of benefit to counteract edema formation.
Abraham
Dietmar
D
Laboratory for Cardiovascular Research, First Department of Anatomy, University of Vienna, Waehringerstrasse 13, A-1090 Vienna, Austria.
Taghavi
Shahrokh
S
Riml
Patricia
P
Paulus
Patrick
P
Hofmann
Michael
M
Baumann
Claudia
C
Kocher
Alfred
A
Klepetko
Walter
W
Aharinejad
Seyedhossein
S
D002199:Capillary Permeability / Q000502:physiology; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology; D016040:Lung Transplantation / Q000502:physiology*; D011652:Pulmonary Circulation / Q000502:physiology*; D011654:Pulmonary Edema / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C
D016228:Endothelial Growth Factors; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C