Gene-eluting stents: adenovirus-mediated delivery of eNOS to the blood vessel wall accelerates re-endothelialization and inhibits restenosis.
Drug-eluting stents for coronary artery disease results in inhibition of smooth muscle cell (SMC) and endothelial cells which may increase the risk of stent thrombosis. In this study, we attempted to enhance re-endothelialization of deployed stents while simultaneously inhibiting intimal hyperplasia by overexpression of endothelial nitric oxide synthase (eNOS) delivery in the vasculature using an adenovirus gene-eluting stent. Re-endothelialization was significantly greater in vessels obtained from normocholesterolemic animals at day 14 (85.34% +/- 7.38 versus 62.66% +/- 10.49; P < 0.05) and day 28 (91.1% +/- 10 versus 63.1% +/- 22; P < 0.05) and hypercholesterolemic animals (96.97% +/- 3.2 versus 28.33% +/- 38.76; P < 0.05) at day 28 with AdeNOS-eluting stents. At day 28, there was a significant increase in the lumen size [AdeNOS 2.73 mm(2) +/- 1.18, AdbetaGal 0.98 mm(2) +/- 0.98, phosphorylcholine (PC) 1.87 mm(2) +/- 1.18; P < 0.05], and a significant reduction in neointimal formation (AdeNOS 2.32 mm(2) +/- 1.13, AdbetaGal 3.73 mm(2) +/- 0.95, PC 3.2 mm(2) +/- 0.94; P < 0.05), and percent restenosis (AdeNOS 45.23 +/- 20.81, AdbetaGal 79.6 +/- 20.31, PC 70.16 +/- 22.2; P < 0.05) in AdeNOS-stented vessels in comparison with controls from hypercholesterolemic animals, assessed by morphometry and quantitative coronary angiography (AdeNOS 15.95% +/- 7.63, AdbetaGal 56.9% +/- 38.6, PC 58 +/- 34.6; P < 0.05). Stent-based delivery of AdeNOS results in enhanced endothelial regeneration and reduction in neointimal formation as compared with controls. This seems to be a promising treatment strategy for preventing in-stent restenosis (ISR) while simultaneously reducing the risk of stent thrombosis.
Sharif
Faisal
F
Regenerative Medicine Institute, National Centre for Biomedical Science Engineering, National University of Ireland, Galway, Ireland.
Hynes
Sean O
SO
Cooney
Ronan
R
Howard
Linda
L
McMahon
Jill
J
Daly
Kieran
K
Crowley
James
J
Barry
Frank
F
O'Brien
Timothy
T
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D023903:Coronary Restenosis / Q000517:prevention & control*; D005822:Genetic Vectors; D006937:Hypercholesterolemia / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011817:Rabbits; D015607:Stents; D017539:Tunica Intima / Q000201:enzymology* / Q000473:pathology
D052250:Nitric Oxide Synthase Type III