Effect of adventitial VEGF(165) gene transfer on vascular thickening after coronary artery balloon injury.
OBJECTIVE
Experimental studies have provided evidence that neovascularization is an important feature of plaque growth, and angiogenic gene therapy may, therefore, increase plaque growth. This study examined the effect of local (peri)adventitial vascular endothelial growth factor165 (VEGF) gene transfer on vascular thickening after coronary balloon injury.


METHODS
Two coronary arteries of 15 pigs were subjected to balloon injury followed by either (peri)adventitial VEGF165 or beta-galactosidase (LacZ) plasmid/liposome-mediated gene transfer via needle injection catheter. At days 3, 14 and 28, histologic sections of coronary arteries were analyzed.


RESULTS
Transferred VEGF165 gene and increased adventitial neovascularization were detected in coronary arteries after balloon injury and VEGF injection. The mean intima+media (I+M) area increased after coronary balloon injury and VEGF (1.13+/-0.17 and 2.54+/-0.52 mm(2)) or LacZ (1.37+/-0.19 and 2.96+/-0.41 mm(2)) gene transfer, with no significant difference between both groups at 3 and 28 days, respectively. No significant difference in I+M neovascularization was observed at day 28 between the treatment groups (microvessel area density 0.24+/-0.08% with VEGF and 0.26+/-0.14% with LacZ, respectively). I+M endothelial cell proliferation index ranged from 7% to 22% (VEGF) and 18% to 24% (LacZ).


CONCLUSIONS
Catheter-mediated (peri)adventitial VEGF165 gene transfer induces adventitial neovascularization but not an increase of vascular thickening/I+M growth and vascularization in a porcine model of coronary artery injury.
Pels
Klaus
K
Department of Cardiology and Pulmology, Charité-University Medicine-Berlin, Germany. kpels@zedat.fu-berlin.de
Deiner
Carolin
C
Coupland
Sarah E
SE
Noutsias
Michel
M
Sutter
Andreas P
AP
Schultheiss
Heinz Peter
HP
Yla-Herttuala
Seppo
S
Schwimmbeck
Peter L
PL
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D002455:Cell Division; D003331:Coronary Vessels / Q000293:injuries* / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D015316:Genetic Therapy / Q000379:methods*; D007267:Injections; D007763:Lac Operon; D023421:Models, Animal; D009389:Neovascularization, Pathologic; D013552:Swine; D014162:Transfection / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A