Bauriedel G, Heidemann P, Klingel K, Windstetter U, Höfling B, Kandolf R
Medizinische Klinik I, Ludwig-Maximilians-Universität München.
Z Kardiol. 1992 Oct;81(10):519-24.
Growth factors and growth factor receptors are considered to be key elements in the pathogenesis of arteriosclerosis and restenosis formation. To study the local expression of epidermal growth factor (EGF) receptor, plaque tissue specimens from advanced lesions (10 coronary, two femoral, seven carotid) of 19 patients were taken for in situ hybridization studies using an EGF-specific cDNA probe. In serial vascular sections of three lesions with increased focal cellularity, autoradiographic silver grains were clearly localized to intimal cells adjacent to the internal elastic lamina. EGF mRNA transcripts were not observed in the fibrous cap, the plaque shoulders, necrotic intimal areas, or in the media. In smooth muscle cells (SMCs) cultured from human plaque tissue, EGF increased SMC proliferative activity in a dose-dependent manner (ED50: 3-6 ng of EGF/ml). Proliferative responsiveness to EGF (10 ng/ml) was found to be significantly (p < 0.01) enhanced in coronary SMCs derived from restenotic lesions as compared to those from primary stenoses. The expression of EGF receptor mRNA in human atheromatous lesions could be of prognostic value to predict an increased SMC proliferative response to stimulatory growth factors.
生长因子和生长因子受体被认为是动脉粥样硬化和再狭窄形成发病机制中的关键因素。为研究表皮生长因子（EGF）受体的局部表达情况，从19例患者的晚期病变（10例冠状动脉、2例股动脉、7例颈动脉）中获取斑块组织标本，使用EGF特异性cDNA探针进行原位杂交研究。在三个局灶性细胞增多的病变的连续血管切片中，放射自显影银颗粒明显定位于紧邻内弹性膜的内膜细胞。在纤维帽、斑块肩部、坏死内膜区域或中膜中未观察到EGF mRNA转录本。在从人斑块组织培养的平滑肌细胞（SMC）中，EGF以剂量依赖性方式增加SMC增殖活性（半数有效剂量：3 - 6 ng EGF/ml）。与来自原发性狭窄的冠状动脉SMC相比，发现来自再狭窄病变的冠状动脉SMC对EGF（10 ng/ml）的增殖反应显著增强（p < 0.01）。人动脉粥样硬化病变中EGF受体mRNA的表达对于预测SMC对刺激性生长因子的增殖反应增加可能具有预后价值。
