Retroviral suicide vector does not inhibit neointimal growth in a porcine coronary model of restenosis.
We attempted to attenuate neointimal formation following vascular injury using a retroviral suicide vector. Epicardial coronary arteries of adult miniature swine were injured by deployment of oversized tantalum stents. One week later, injured segments were exposed to packaged retroviral constructs with or without the herpes simplex virus thymidine kinase gene. Ganciclovir treatments were initiated 48 hours later in both control and experimental swine and continued for two weeks. Four weeks following vascular injury, both control and experimental arteries were harvested and histologically prepared for image analysis. Despite adequate marker gene expression, there was no significant difference in the neointimal area or neointimal/media ratio between control and experimental groups. While the HSVtk ganciclovir system attenuates cell proliferation in other systems, retroviral vector targeting of vascular smooth muscle cells for elimination may be too inefficient to prevent restenosis following angioplasty.
Barbee
R W
RW
Department of Internal Medicine, Alton Ochsner Medical Institutions, New Orleans, Louisiana.
Stapleton
D D
DD
Madras
D E
DE
Ré
R N
RN
Murgo
J P
JP
Davenport
W D
WD
Giardina
J
J
Cook
J L
JL
D000818:Animals; D002460:Cell Line; D003327:Coronary Disease / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D015774:Ganciclovir / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D008156:Luciferases / Q000096:biosynthesis; D008297:Male; D011994:Recombinant Proteins / Q000096:biosynthesis; D012008:Recurrence; D012190:Retroviridae; D018139:Simplexvirus / Q000235:genetics; D015607:Stents; D013552:Swine; D013556:Swine, Miniature; D013635:Tantalum; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology*
D011994:Recombinant Proteins; D013635:Tantalum; D008156:Luciferases; D013937:Thymidine Kinase; D015774:Ganciclovir