title: Early cell loss after angioplasty results in a disproportionate decrease in percutaneous gene transfer to the vessel wall.
abstract: Acute cell loss has been documented following angioplasty of normal rat and rabbit arteries. Here we analyzed the effects of balloon injury intensity on early cellular loss in single- and double-injury models and how it influences the efficiency of percutaneous gene delivery to the vessel wall. Rabbits underwent bilateral iliac angioplasties (n = 52) with 2.5-mm (balloon-to-artery [B/A] ratio, 1.08 to 1.13) and 3.0-mm (B/A ratio, 1.29 to 1.34) balloons. In the single-injury model, the 3.0-mm balloon induced a 61% reduction in medial cellularity at 3 days postinjury (p < 0.001) while the 2.5-mm balloon did not produce significant cell loss. In the double-injury model, the effects were more pronounced, with 35% (p < 0.01) and 91% (p < 0.001) reductions in medial cellularity at 3 days with the 2.5- and 3.0-mm balloons, respectively, but neointimal cellularity was decreased only with the 3.0-mm balloon (37% reduction, p = 0.025). Adenovirus-mediated beta-galactosidase gene delivery with a channel balloon (n = 24) revealed that larger balloon-to-artery ratios decreased both absolute levels and relative frequencies of transgene expression in the vessel wall. In the single-injury model, gene transfer efficiency was 4.2+/-1.1 and 1.3+/-0.25% (p < 0.05) for the small and large balloons, respectively. In the double-injury model, gene transfer efficiency was 6.6+/-1.6 and 2.3+/-0.8% (p < 0.05) in the neointima and 4.1+/-1.2 and 2.6+/-1.2% (p = NS) in the media for the small and large balloon, respectively. We conclude that early cell loss is dependent on the intensity of the injury in both single- and double-injury models of balloon angioplasty, with greater frequencies of cell loss occurring in the media than in the neointima. In both models, larger balloon-to-artery ratios result in disproportionate reductions in percutaneous adenovirus-mediated gene delivery.
authors: Division of Cardiovascular Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135-2997, USA.
authors: A
authors: A
authors: Rivard
authors: Z
authors: Z
authors: Luo
authors: H
authors: H
authors: Perlman
authors: J E
authors: JE
authors: Fabre
authors: T
authors: T
authors: Nguyen
authors: L
authors: L
authors: Maillard
authors: K
authors: K
authors: Walsh
mesh_terms: D000256:Adenoviridae; D000279:Administration, Cutaneous; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D016923:Cell Death; D017023:Coronary Angiography; D004730:Endothelium, Vascular / Q000378:metabolism*; D018014:Gene Transfer Techniques; D007083:Iliac Artery / Q000033:anatomy & histology / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D011817:Rabbits; D013997:Time Factors