Altered expression of vascular endothelial growth factor and its receptors in normal saphenous vein and in arterialized and stenotic vein grafts.
BACKGROUND
Myointimal thickening is a major cause saphenous vein graft failure. The prominence of medial and adventitial microvessels in stenotic vein grafts and the known angiogenic effects of vascular endothelial growth factor (VEGF) lead us to investigate the expression of VEGF and its receptors in vein graft arterialization and stenosis.


METHODS
Normal and arterialized vein graft segments were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) for expression of VEGF-R1 (flt), VEGF-R2 (KDR), and neuropilin-1. The cells expressing VEGF, VEGF-R1, VEGF-R2, and neuropilin-1 were identified in normal, stenotic, and arterialized vein graft segments by immunohistochemistry.


RESULTS
Vascular endothelial growth factor, detected in the wall in endothelial cells and adventitial microvessels in normal vein, localized to smooth muscle cells, endothelial cells and adventitial microvessels in arterialized and stenotic vein. VEGF-R1 and VEGF-R2 were expressed infrequently on endothelial cells, macrophages, and smooth muscle cells in arterialized and stenotic vein. Neuropilin-1 was detected in all specimens. RT-PCR demonstrated significantly greater expression of neuropilin-1 in normal vein compared with arterialized vein (P <0.05).


CONCLUSIONS
The differential expression of VEGF and its receptors in normal, arterialized, and stenotic vein grafts suggests that alterations in VEGF/VEGF-R2/neuropilin-1 interactions may be important determinants of the adaptive response of vein grafts to arterialization.
Department of Surgery, Division of Vascular Surgery, University of Texas Medical Branch, 6.110 JSA 0541, 301 University Boulevard, Galveston, TX 77555-0541, USA.
Kenneth J
KJ
Woodside
Joseph J
JJ
Naoum
Ronald J
RJ
Torry
Xiang Y
XY
Xue
Ann S
AS
Burke
Lyuba
L
Levine
John A
JA
Daller
Glenn C
GC
Hunter
D006083:Graft Occlusion, Vascular / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D039942:Neuropilin-1 / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012501:Saphenous Vein / Q000378:metabolism / Q000637:transplantation*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040262:Receptors, Vascular Endothelial Growth Factor