Characterization of a new double-injury restenosis model in the rat aorta

To characterize a new rat model of restenosis for evaluation of local or systemic drug strategies.

Arterial lesions were induced by placement of silicone cuffs around the aorta of Lewis rats. After 21 days, the cuffs were removed, and a subgroup of rat aortas was subjected to secondary balloon injury. Remodeling of wall compartments and cell kinetics were assessed morphometrically at 3, 7, 14, 21, and 28 days after the single and double-injury approaches. Immunohistochemistry was used to assess the distribution of macrophages, smooth muscle cells, and proliferating cells within the layers of the arterial wall in the experimental groups versus sham-operated and untreated controls.

After cuff placement, the adventitia initially undergoes significant enlargement, while the media shows a reduction in relative thickness. Accumulation of cells within the adventitia at 3 and 7 days is followed by a marked decline in cell density at 14 days, with simultaneously increasing cell numbers in the intima. At this time, activated macrophages are detected in the adventitia, indicating chronic inflammation. Following cuff placement, mild intimal hyperplasia develops. In the double-injury model, extensive neointimal hyperplasia forms rapidly, with a peak at 14 days.

This new double-injury model is technically easy, and multiple experiments can be accrued in short periods of time. It provides an additional platform to identify new targets and strategies for the prophylaxis of postangioplasty restenosis.