TY - JOUR
T1 - Gene transfer to coronary artery bypass conduits
AU - Chiu-Pinheiro, Cynthia K.
AU - O'Brien, Timothy
AU - Katusic, Zvonimir S.
AU - Bonilla, Luis F.
AU - Hamner, Chad E.
AU - Schaff, Hartzell V.
N1 - Funding Information:
We thank William J. Anding, Marilyn R. Oeltjen, Sharon A. Stephan, Rebecca M. Wilson, and Tyra A. Witt for their technical assistance. This study was supported by a gift from Mr. and Mrs. Tomas Furth, the Mayo Molecular Medicine Research Award, and research grant HL58080 (TOB) from the National Institutes of Health.
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Background. Gene therapy is a rational approach to prevention of stenosis in saphenous vein grafts used as conduits for coronary artery bypass grafting. To explore this possibility we developed methods for adenoviral-mediated gene transfer to canine saphenous veins. Methods. During a single procedure, autogenous canine saphenous vein segments were transduced ex vivo and used as coronary artery bypass grafts. The proximal end of each vein was ligated, adenovirus containing the Escherichia coli β-galactosidase gene (Ad.CMVLacZ) was delivered at titers of 2.5 × 109 or 5 × 109 plaque-forming units (pfu)/mL to the lumen through a distal heparin lock, and the segment was immersed in the viral solution for 1 hour at 37°C. Control segments were exposed to diluent alone in an identical manner. Aortocoronary anastomoses were made using cardiopulmonary bypass. Transgene expression was assessed qualitatively and quantitatively after 3 days. Results. β-Galactosidase levels showed a dose-dependent increase: 0.00 ± 0.00 ng/mg total protein for controls; 5.60 ± 2.27 ng/mg total protein for a viral titer of 2.5 × 109 pfu/mL and 11.97 ± 6.14 ng/mg for 5 × 109 pfu/mL. The two dosage groups differed significantly from each other (p = 0.035) and from controls (p = 0.003). X-gal staining demonstrated mostly endothelial and scattered adventitial transgene expression. Conclusions. Transgene expression after ex vivo gene transfer into saphenous vein grafts in a canine coronary artery bypass model indicates that this method may be useful for delivery of therapeutic genes to prevent or retard vein graft arteriosclerosis.
AB - Background. Gene therapy is a rational approach to prevention of stenosis in saphenous vein grafts used as conduits for coronary artery bypass grafting. To explore this possibility we developed methods for adenoviral-mediated gene transfer to canine saphenous veins. Methods. During a single procedure, autogenous canine saphenous vein segments were transduced ex vivo and used as coronary artery bypass grafts. The proximal end of each vein was ligated, adenovirus containing the Escherichia coli β-galactosidase gene (Ad.CMVLacZ) was delivered at titers of 2.5 × 109 or 5 × 109 plaque-forming units (pfu)/mL to the lumen through a distal heparin lock, and the segment was immersed in the viral solution for 1 hour at 37°C. Control segments were exposed to diluent alone in an identical manner. Aortocoronary anastomoses were made using cardiopulmonary bypass. Transgene expression was assessed qualitatively and quantitatively after 3 days. Results. β-Galactosidase levels showed a dose-dependent increase: 0.00 ± 0.00 ng/mg total protein for controls; 5.60 ± 2.27 ng/mg total protein for a viral titer of 2.5 × 109 pfu/mL and 11.97 ± 6.14 ng/mg for 5 × 109 pfu/mL. The two dosage groups differed significantly from each other (p = 0.035) and from controls (p = 0.003). X-gal staining demonstrated mostly endothelial and scattered adventitial transgene expression. Conclusions. Transgene expression after ex vivo gene transfer into saphenous vein grafts in a canine coronary artery bypass model indicates that this method may be useful for delivery of therapeutic genes to prevent or retard vein graft arteriosclerosis.
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U2 - 10.1016/S0003-4975(02)03831-6
DO - 10.1016/S0003-4975(02)03831-6
M3 - Article
C2 - 12400762
AN - SCOPUS:0036797985
SN - 0003-4975
VL - 74
SP - 1161
EP - 1166
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 4
ER -