RESUMO
Expandable intra-arterial stents are widely used for treating coronary disease. We hypothesized that local gene delivery could be achieved with the controlled release of DNA from a polymer coating on an expandable stent. Our paper reports the first successful transfection in vivo using a DNA controlled-release stent. Green fluorescent protein (GFP) plasmid DNA within emulsion-coated stents was efficiently expressed in cell cultures (7.9% +/- 0.7% vs. 0.6% +/- 0.2% control, p < 0.001) of rat aortic smooth muscle cells. In a series of pig stent-angioplasty studies, GFP expression was observed in all coronary arteries (normal, nondiseased) in the DNA-treated group, but not in control arteries. GFP plasmid DNA in the arterial wall was confirmed by PCR, and GFP presence in the pig coronaries was confirmed by immunohistochemistry. Thus, DNA-eluting stents are capable of arterial transfection, and could be useful as delivery systems for candidate vectors for gene therapy of cardiovascular diseases.
Assuntos
Vasos Coronários/patologia , Técnicas de Transferência de Genes , Stents , Animais , Benzotiazóis , Doenças Cardiovasculares/terapia , Células Cultivadas , DNA/farmacocinética , Eletroforese em Gel de Ágar , Corantes Fluorescentes , Proteínas de Fluorescência Verde , Imuno-Histoquímica , Cinética , Proteínas Luminescentes/metabolismo , Masculino , Músculo Liso/citologia , Músculo Liso/metabolismo , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase , Quinolinas , Ratos , Suínos , Tiazóis , Fatores de Tempo , TransfecçãoRESUMO
Percutaneous intervention for the first episode of in-stent restenosis was performed in 177 patients 5.4 +/- 0.3 months after native coronary stent implantation. Medical records were reviewed and patients contacted 13.3 +/- 1.2 months after in-stent intervention to ascertain the subsequent clinical course. The effects of demographic, procedural, and angiographic variables on clinical outcomes were determined. At 2 years, Kaplan-Meier estimated survival was 93 +/- 3% and freedom from death, myocardial infarction, and a third target artery revascularization (TAR) was 67 +/- 4%. The actuarial frequency of a third TAR was 26 +/- 4% at 1 year. Stratification of outcomes according to timing of in-stent intervention revealed an approximate twofold higher frequency of adverse events among patients with early (=3 months) in-stent restenosis. Advanced age (p = 0.019), prior coronary bypass (p = 0. 017), and early in-stent intervention (p = 0.006) independently predicted increased mortality at follow-up. Systemic hypertension (p = 0.004), diabetes mellitus (p = 0.044), and early in-stent intervention (p <0.0001) independently predicted a third TAR. These variables (p = 0.007, p = 0.027, and p <0.0001, respectively) also independently predicted a composite end point consisting of death, myocardial infarction, and a third TAR. No angiographic variable predicted outcome after in-stent intervention. Thus, long-term outcome following in-stent intervention was favorable. Early in-stent intervention, advanced age, hypertension, and diabetes predicted adverse outcomes.