© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Effect of adventitial VEGF165 gene transfer on vascular thickening after coronary artery balloon injury
aDepartment of Cardiology and Pulmology, Charité-University Medicine-Berlin, Joint Facility of the Freie Universität Berlin and the Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany
bDepartment of Pathology, Charité-University Medicine-Berlin, Joint Facility of the Freie Universität Berlin and the Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany
cDepartment of Gastroenterology, Charité-University Medicine-Berlin, Joint Facility of the Freie Universität Berlin and the Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany
dAI Virtanen Institute and Department of Medicine, University of Kupio, Kupio, Finland
*Corresponding author. Tel.: +49-30-8445-2344; fax: +49-30-8445-4648. Email address: kpels{at}zedat.fu-berlin.de
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 β-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 mm2) or LacZ (1.37±0.19 and 2.96±0.41 mm2) 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.
KEYWORDS Angiogenesis; Atherosclerosis; Gene therapy; Growth factors