Adventitial VEGF165 gene transfer prevents lumen loss through induction of positive arterial remodeling after PTCA in porcine coronary arteries.
Negative arterial remodeling still plays an important role in the pathogenesis of coronary restenosis even in the era of interventional stenting (e.g. arterial narrowing occurs proximal and distal of a stented segment). Previous studies suggest that increased angiogenesis and inhibited regression of injury-induced adventitial microvessels prevents negative remodeling. We have examined the effect of local vascular endothelial growth factor (VEGF(165)) gene transfer on adventitial microvessel angiogenesis/regression and arterial remodeling after coronary angioplasty. Twenty pigs underwent angioplasty, each one in two major coronary arteries, followed by plasmid liposome gene transfer with either VEGF(165) or control gene LacZ (50 microg DNA with 50 microg of Lipofectine) into the (peri)adventitial space using a needle injection catheter. Arteries were examined at days 1, 7, 14, and 28. Local delivery of VEGF(165) gene into the outer compartments of balloon-injured porcine coronary arteries reduced lumen area loss due to distinct positive remodeling (arterial enlargement). Prevention of adventitial microvessel regression, enhanced adventitial elastin accumulation, reduced adventitial myofibroblast numbers, and a pronounced adventitial inflammatory response considered as a part of arterial healing seem to be the main VEGF-mediated mechanisms indicating the therapeutic potential of VEGF for restenosis prevention.
Deiner
Carolin
C
Department of Cardiology, Charité-Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
Schwimmbeck
Peter Lothar
PL
Koehler
Ina Sabine
IS
Loddenkemper
Christoph
C
Noutsias
Michel
M
Nikol
Sigrid
S
Schultheiss
Heinz-Peter
HP
Ylä-Herttuala
Seppo
S
Pels
Klaus
K
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D023903:Coronary Restenosis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000473:pathology*; D004195:Disease Models, Animal; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A