HISTOLOGICAL EXMINATION OF CELL CYCLE REGULATOR EXPRESSION AFTER CORONARY STENTING

背景血管平滑肌细胞(VSMCs)的增殖受多种生长因子诱导的细胞周期调节活性的调控。最近，针对细胞周期调节因子的治疗已经引起了人们的注意，以防止冠状动脉血管成形术后VSMCs的增殖。然而，对人冠状动脉支架置入后细胞周期调节因子表达的组织病理学评价还不够。方法与结果对27例身体36支冠状动脉进行了检测。从支架置入到患者死亡的时间为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。用巨噬细胞集落刺激因子受体(MCSF-R)染色检测再分化的VSMCs。在新生内膜可见MCSF-R阳性细胞，但在晚期阳性细胞减少。PDGF在新生内膜中表达，并呈逐渐下降趋势。细胞周期蛋白D1的表达与VSMCs的增殖有关，而p27的表达随着血管内皮细胞的增殖而下调，晚期上调。结论限制p27的表达或抑制细胞周期蛋白D1的表达是预防支架术后新生内膜过度增殖的最有前景的方法之一。

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.