HISTOLOGICAL EXMINATION OF CELL CYCLE REGULATOR EXPRESSION AFTER CORONARY STENTING

背景血管平滑肌细胞（vascular smooth muscle cells，VSMCs）的增殖受细胞周期调控因子的调控，而细胞周期调控因子的活性受多种生长因子的诱导。最近的注意力已经被吸引到靶向细胞周期调节剂以防止冠状动脉成形术后VSMCs增殖的治疗上。然而，人类冠状动脉支架植入术后细胞周期调节因子表达的组织病理学评价还不够充分。方法和结果36冠状动脉27具尸体进行了检查。从支架植入到患者死亡的时间范围为0 - 235天。切片用抗血小板衍生生长因子（PDGF）、碱性成纤维细胞生长因子（b-FGF）、细胞周期蛋白D1、p16、p21和p27的抗体染色。巨噬细胞集落刺激因子受体（MCSF-R）染色检测再分化的血管平滑肌细胞，MCSF-R阳性细胞在新生内膜可见，但在晚期减少。PDGF在新生内膜中表达，并逐渐减少。cyclin D1的表达与血管平滑肌细胞的增殖有关，而p27的表达随着血管内膜的增殖而下调，并在血管内膜增生的晚期上调。结论我们的研究结果表明，限制p27的下降或cyclin D1的升高是预防支架术后血管内膜过度增殖的最有希望的方法之一。

Background Proliferation of vascular smooth muscle cells (VSMCs) is under the control of cell cycle regulator activity, which is induced by several growth factors. Recent attention has been drawn to treatments that target cell cycle regulators to prevent the proliferation of VSMCs after coronary angioplasty. However, histopathological evaluation of cell cycle regulator expression after human coronary stenting has not been sufficient.Methods and Results Thirty-six coronary arteries of 27 cadavers were examined. Time from stent implantation to patient death ranged from 0 to 235 days. Sections were stained with antibodies against platelet-derived growth factor (PDGF), basic fibroblast growth factor (b-FGF), cyclin D1, p16, p21, and p27. To detect redifferentiated VSMCs, staining for macrophage colony stimulating factor receptor (MCSF-R) was done.MCSF-R-positive cells were observed in neointima but decreased in the late stage. PDGF was detected in neointima and decreased gradually. Expression of cyclin D1 appeared to be associated with the proliferation of VSMCs, whereas p27 was downregulated with the proliferation of neointima and upregulated in the late stage.Conclusions Our results suggest that one of the most promising methods for preventing excessive proliferation of neointima after stenting is to limit the decrease of p27 or the increase of cyclin D1.