Vascular endothelial growth factor (VEGF165) and its influence on angiogenesis versus arteriogenesis in different vascular beds.
OBJECTIVE
To use local gene delivery to determine any district-specific influence of vascular endothelial growth factor (VEGF(165)) on angiogenesis and arteriogenesis in arteries of distinct developmental origin.


METHODS
Coronary and peripheral arteries were chronically occluded in 30 Pietrain pigs using a percutaneous approach and blinded stent-graft. DNA was delivered to the adventitia in dosages corresponding to 10% of the body weight-adapted amount used in clinical trials. The coronary arteries in 12 animals and the peripheral arteries in 12 animals were treated or used as controls (no occlusion or occlusion with transfection of the beta-galactosidase gene). Six additional animals were sacrificed at 1 or 3 weeks for expression analyses, while the other 24 animals were sacrificed at 5 months for expression analysis and histology. Angiography, polymerase chain reaction analyses, and immunohistochemistry were performed.


RESULTS
Expression of the VEGF gene was observed at 1 and 3 weeks following application, while transfected DNA was detected up to 5 months. New collaterals formed around occluded coronary arteries (2.63 +/- 0.69 fold, p<0.05 versus 1.24 +/- 0.40 fold for peripheral arteries), and angiographic arterial area increase was more pronounced in coronary (2.49 +/- 0.59 fold, p<0.05) than peripheral arteries (1.49 +/- 0.05 fold). There was no collateralization surrounding occluded peripheral arteries, but new arterial branches were seen (2.0 +/- 0.28, p<0.05 versus 1.07 +/- 0.31 for coronary).


CONCLUSIONS
The response to VEGF, whether it is predominantly angiogenesis or arteriogenesis, is dependent on the target vessel. These observed differences in the behavior of arteries may be related to their differing developmental origins, which may have important implications for future therapeutic strategies using VEGF in different vessels.
Nikol
Sigrid
S
Medical Clinic I, Klinikum Grosshadern, Germany. nikol@uni-muenster.de
Pelisek
Jaroslav
J
Engelmann
Markus G
MG
Shimizu
Masumi
M
Fuchs
Alexandra
A
Golda
Adam
A
Armeanu
Sorin
S
Mekkaoui
Choukri
C
Rolland
Pierre H
PH
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism; D018014:Gene Transfer Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000627:therapeutic use; D008222:Lymphokines / Q000235:genetics* / Q000627:therapeutic use; D008955:Models, Cardiovascular; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics*; D016491:Peripheral Vascular Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics; D010957:Plasmids / Q000235:genetics / Q000627:therapeutic use; D011859:Radiography; D013552:Swine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors