De Meyer Simon F, Staelens Stephanie, Badenhorst Philip N, Pieters Henry, Lamprecht Seb, Roodt Jan, Janssens Stefan, Meiring Muriel, Vanhoorelbeke Karen, Bruwer André, Brown Stephen, Deckmyn Hans
Laboratory for Thrombosis Research, I.R.C., KULeuven Campus Kortrijk, E. Sabbelaan 53, 8500 Kortrijk, Belgium.
Thromb Haemost. 2007 Dec;98(6):1343-9. doi: 10.1160/th07-05-0335.
Revascularization techniques, such as angioplasty and stent implantation, frequently lead to restenosis due to the formation of neointima after platelet activation and the concomitant release of various smooth muscle cell mitogenic and attractant factors. We here investigate whether inhibition of initial platelet adhesion after stent implantation can decrease neointima formation in a clinically relevant baboon model of in-stent stenosis using standard treatment with aspirin, clopidogrel and heparin. Inhibition of platelet adhesion was established by administration of the anti-von Willebrand factor (VWF) monoclonal antibody 82D6A3, which inhibits VWF binding to collagen. Administration of 82D6A3 resulted in a complete inhibition of VWF binding to collagen during the first three days after stent implantation. No thrombocytopenia or prolongation of the bleeding time was observed. Our results show that the formation of neointima was not affected in the group of baboons where primary platelet adhesion was abolished with 82D6A3 when compared to the control group. Vascular injury scores were the same in both groups. Inhibition of platelet adhesion during the first three days after stenting, on top of standard treatment with aspirin, clopidogrel and heparin, had no effect on neo-intima formation in a baboon model of in-stent stenosis. During the last decade, attempts to translate seemingly effective therapies based on smaller animal experimentation to the clinic have consistently failed. This study, using a non-human primate model that more closely resembles the clinical situation, presents a model that may be of further clinical interest for studying the prevention of restenosis.
血管重建技术，如血管成形术和支架植入术，由于血小板激活后新生内膜的形成以及随之释放的各种平滑肌细胞促有丝分裂和趋化因子，常常导致再狭窄。我们在此研究在使用阿司匹林、氯吡格雷和肝素进行标准治疗的情况下，抑制支架植入后初始血小板黏附是否能减少临床相关狒狒支架内狭窄模型中的新生内膜形成。通过给予抗血管性血友病因子（VWF）单克隆抗体82D6A3来抑制血小板黏附，该抗体可抑制VWF与胶原蛋白的结合。给予82D6A3可在支架植入后的头三天完全抑制VWF与胶原蛋白的结合。未观察到血小板减少或出血时间延长。我们的结果表明，与对照组相比，在使用82D6A3消除原发性血小板黏附的狒狒组中，新生内膜的形成未受影响。两组的血管损伤评分相同。在阿司匹林、氯吡格雷和肝素标准治疗基础上，在支架植入后的头三天抑制血小板黏附，对狒狒支架内狭窄模型中的新生内膜形成没有影响。在过去十年中，将基于小型动物实验的看似有效的治疗方法转化到临床的尝试一直失败。这项研究使用了更接近临床情况的非人类灵长类动物模型，提供了一个可能对研究再狭窄预防具有进一步临床意义的模型。
