Bauriedel G, Ganesh S, Uberfuhr P, Welsch U, Höfling B
Medizinische Klinik I, Ludwig-Maximilians-Universität München.
Z Kardiol. 1992 Feb;81(2):92-8.
Proliferative, migratory, and secretory activities of vascular smooth muscle cells are currently discussed as determinants of human plaque and restenosis formation. Affecting these determinants with drugs may promise anti-arteriosclerotic effects. Plaque tissue was removed from both coronary and peripheral lesions of a total of 18 patients to cultivate smooth muscle cells (SMC) for subsequent in vitro studies. The antitubulin colchicine (C) caused a concentration-dependent decrease of SMC proliferative activity with an IC50 of 5 x 10(-9) M. Migratory activity was analyzed by a standardized semi-automatic video system. This parameter was reduced by C in a concentration-dependent manner (IC50: 5 x 10(-10) M). As shown by immunofluorescence microscopy, the typical structure of microtubules of C-treated SMCs was distorted, whereas the pattern of alpha-actin filaments remained unaltered. Transmission electron microscopy (TEM) revealed that the number of microtubules was diminished after addition of C, and that a distinct disorganization of cytoplasmic organelles as well as the formation of vacuoles had occurred. In vitro studies of human smooth muscle cells derived from vascular plaques indicate that colchicine may be useful as an anti-arteriosclerotic drug, since a concentration-dependent concordant effect on proliferation, migration, and secretory processes of the SMC could be demonstrated.
血管平滑肌细胞的增殖、迁移和分泌活动目前被认为是人类斑块和再狭窄形成的决定因素。用药物影响这些决定因素可能有望产生抗动脉粥样硬化作用。从总共18例患者的冠状动脉和周围病变中取出斑块组织，培养平滑肌细胞（SMC）用于后续的体外研究。抗微管蛋白秋水仙碱（C）导致SMC增殖活性呈浓度依赖性降低，IC50为5×10（-9）M。迁移活性通过标准化的半自动视频系统进行分析。该参数被C以浓度依赖性方式降低（IC50：5×10（-10）M）。免疫荧光显微镜显示，用C处理的SMC微管的典型结构发生扭曲，而α-肌动蛋白丝的模式保持不变。透射电子显微镜（TEM）显示，加入C后微管数量减少，并且发生了细胞质细胞器的明显紊乱以及液泡的形成。对源自血管斑块的人平滑肌细胞的体外研究表明，秋水仙碱可能作为一种抗动脉粥样硬化药物有用，因为可以证明对SMC的增殖、迁移和分泌过程具有浓度依赖性的协同作用。
