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Early cell loss after angioplasty results in a disproportionate decrease in percutaneous gene transfer to the vessel
1Division of Cardiovascular Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135-2997, USA.
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.
Insights
Balloon angioplasty intensity significantly impacts early arterial cell loss and reduces gene delivery efficiency. Higher balloon-to-artery ratios cause more cell loss and less effective percutaneous gene transfer in rabbit iliac arteries.
Area of Science:
- Vascular Biology
- Interventional Cardiology
- Gene Therapy
Background:
- Acute cell loss is a known complication after angioplasty in normal arteries.
- Understanding the impact of injury intensity on cell loss and gene delivery is crucial for optimizing procedures.
Purpose of the Study:
- To analyze the effects of varying balloon angioplasty injury intensity on early cellular loss.
- To investigate how injury intensity influences the efficiency of percutaneous gene delivery to the vessel wall.
Main Methods:
- Rabbits (n=52) underwent single- and double-injury iliac angioplasties using different balloon-to-artery (B/A) ratios (2.5-mm and 3.0-mm balloons).
- Medial and neointimal cellularity were assessed at 3 days post-injury.
- Adenovirus-mediated beta-galactosidase gene delivery was performed (n=24) to evaluate transgene expression efficiency.
Main Results:
- The 3.0-mm balloon (higher B/A ratio) caused significant medial cell loss (61% in single, 91% in double injury) compared to the 2.5-mm balloon.
- Double injury exacerbated cell loss, particularly in the media.
- Larger B/A ratios significantly reduced adenovirus-mediated gene transfer efficiency in both single and double injury models.
Conclusions:
- Early cell loss following balloon angioplasty is directly dependent on injury intensity.
- Greater cell loss occurs in the media compared to the neointima.
- Increased balloon-to-artery ratios impair percutaneous gene delivery efficiency.