Kollum M, Kaiser S, Kinscherf R, Metz J, Kübler W, Hehrlein C
Department of Cardiology, University of Heidelberg, Germany.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2383-8. doi: 10.1161/01.atv.17.11.2383.
Both cell proliferation and apoptosis (programmed cell death) are supposed to play a role in restenosis after angioplasty. We studied these processes in smooth muscle cells (SMCs) and macrophages 1, 4, and 12 weeks after balloon angioplasty or Palmaz-Schatz stent implantation in rabbit iliac arteries. Proliferating cells were visualized by immunostaining with antibodies directed against proliferating cell nuclear antigen. Apoptotic cells were detected using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling) technique, propidium iodide staining, and transmission electron microscopy. At all time points, the neointimal cross-sectional area of the arteries was twofold to fourfold greater after stent implantation than after balloon angioplasty. The total number of neointimal cells was similar 1 and 12 weeks after both interventions. The neointimal cell density, however, decreased by 58% between the 1st and the 12th week after stent implantation compared with a 20% decrease after balloon angioplasty (P < .01). Stent implantation induced more cell proliferation but also more apoptosis in the media than balloon angioplasty after 1 and 4 weeks. In addition, stent implantation caused more macrophage accumulation and apoptosis in the neointima, but cell proliferation rates did not differ significantly in comparison with balloon angioplasty. The higher rate of apoptosis in the neointima 1 week after stent implantation compared with balloon angioplasty is due to an increased rate of SMC and macrophage death. Macrophage accumulation and apoptosis in the early phase after stent implantation appear to play a role in extracellular matrix secretion, which increases neointima formation after 4 and 12 weeks compared with balloon angioplasty in this model.
细胞增殖和细胞凋亡（程序性细胞死亡）均被认为在血管成形术后再狭窄过程中发挥作用。我们在兔髂动脉进行球囊血管成形术或植入Palmaz-Schatz支架后1周、4周和12周，对平滑肌细胞（SMC）和巨噬细胞中的这些过程进行了研究。通过用针对增殖细胞核抗原的抗体进行免疫染色来观察增殖细胞。使用TUNEL（末端脱氧核苷酸转移酶介导的dUTP缺口末端标记）技术、碘化丙啶染色和透射电子显微镜检测凋亡细胞。在所有时间点，支架植入后动脉的新生内膜横截面积比球囊血管成形术后大2至4倍。两种干预后1周和12周，新生内膜细胞总数相似。然而，与球囊血管成形术后20%的下降相比，支架植入后第1周和第12周之间新生内膜细胞密度下降了58%（P<.01）。在1周和4周后，与球囊血管成形术相比，支架植入在中膜诱导了更多的细胞增殖，但也诱导了更多的细胞凋亡。此外，支架植入导致新生内膜中巨噬细胞积聚和凋亡增加，但与球囊血管成形术相比，细胞增殖率无显著差异。与球囊血管成形术相比，支架植入后1周新生内膜中较高的凋亡率是由于SMC和巨噬细胞死亡率增加所致。在该模型中，支架植入后早期巨噬细胞的积聚和凋亡似乎在细胞外基质分泌中起作用，与球囊血管成形术相比，这在4周和12周后增加了新生内膜的形成。
