Intravascular local gene transfer mediated by protein-coated metallic stent.
OBJECTIVE
To assess the feasibility, efficiency and selectivity of adenovirus-mediated gene transfer to local arterial wall by protein-coated metallic stent.


METHODS
A replication-defective recombinant adenovirus carrying the Lac Z reporter gene for nuclear-specific beta-galactosidase (Ad-beta gal) was used in this study. The coating for metallic stent was made by immersing it in a gelatin solution containing crosslinker. The coated stents were mounted on a 4.0 or 3.0 mm percutaneous transluminal coronary angioplasty (PTCA) balloon and submersed into a high-titer Ad-beta gal viral stock (2 x 10(10) pfu/ml) for 3 min, and then implanted into the carotid arteries in 4 mini-swines and into the left anterior descending branch of the coronary artery in 2 mini-swines via 8F large lumen guiding catheters. The animals were sacrificed 7 (n = 4), 14 (n = 1) and 21 (n = 1) days after implantation, respectively. The beta-galactosidase expression was assessed by X-gal staining.


RESULTS
The results showed that the expression of transgene was detected in all animal. In 1 of carotid artery with an intact intima, the beta-gal expression was limited to endothelial cells. In vessels with denuded endothelium, gene expression was found in the sub-intima, media and adventitia. The transfection efficiency of medial smooth muscle cells was 38.6%. In 2 animals sacrificed 7 days after transfection, a microscopic examination of X-gal-stained samples did not show evidence of transfection in remote organs and arterial segments adjacent to the treated arterial site.


CONCLUSIONS
Adenovirus-mediated arterial gene transfer to endothelial, smooth muscle cells and adventitia by protein-coated metallic stent is feasible. The transfection efficiency is higher. The coated stent may act as a good carrier of adenovirus-mediated gene transfer and have a potential to prevent restenosis following PTCA.
Yuan
J
J
Department of Coronary Heart Disease, Cardiovascular Institute & Fu Wai Hospital, CAMS, PUMC, Beijing 100037, China.
Gao
R
R
Shi
R
R
Song
L
L
Tang
J
J
Li
Y
Y
Tang
C
C
Meng
L
L
Yuan
W
W
Chen
Z
Z
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005260:Female; D018014:Gene Transfer Techniques; D008297:Male; D015607:Stents; D013552:Swine; D013556:Swine, Miniature; D014162:Transfection; D019076:Transgenes; D001616:beta-Galactosidase / Q000235:genetics*
D001616:beta-Galactosidase