APOPTOSIS AFTER STENT IMPLANTATION COMPARED WITH BALLOON ANGIOPLASTY IN RABBITS - ROLE OF MACROPHAGES

Both cell proliferation and apoptosis (programmed cell death) are supp osed to play a role in restenosis after angioplasty. We studied these processes in smooth muscle cells (SMCs) and macrophages 1, 4, and 12 w eeks after balloon angioplasty or Palmaz-Schatz stent implantation in rabbit iliac arteries. Proliferating cells were visualized by immunost aining with antibodies directed against proliferating cell nuclear ant igen. Apoptotic cells were detected using the TUNEL (terminal deoxynuc leotidyl transferase-mediated dUTP nick end labeling) technique, propi dium iodide staining, and transmission electron microscopy. At all tim e points, the neointimal cross-sectional area of the arteries was twof old to fourfold greater after stent implantation than after balloon an gioplasty. The total number of neointimal cells was similar 1 and 12 w eeks after both interventions. The neointimal cell density, however, d ecreased by 58% between the 1st and the 12th week after stent implanta tion compared with a 20% decrease after balloon angioplasty (P<.01). S tent implantation induced more cell proliferation but also more apopto sis in the media than balloon angioplasty after 1 and 4 weeks. In addi tion, stent implantation caused more macrophage accumulation and apopt osis in the neointima, but cell proliferation rates did not differ sig nificantly in comparison with balloon angioplasty. The higher rate of apoptosis in the neointima 1 week after stent implantation compared wi th balloon angioplasty is due to an increased rate of SMC and macropha ge death. Macrophage accumulation and apoptosis in the early phase aft er stent implantation appear to play a role in extracellular matrix se cretion, which increases neointima formation after 4 and 12 weeks comp ared with balloon angioplasty in this model.