Voisard R, Seitzer U, Baur R, Dartsch P C, Osterhues H, Höher M, Hombach V
Department of Cardiology, Angiology, Nephrology, and Pneumology, University of Ulm, Federal Republic of Germany.
Int J Cardiol. 1995 Aug;51(1):15-28. doi: 10.1016/0167-5273(95)02377-9.
Recent advances in the understanding of the biology of restenosis indicate that it is predominantly caused by a multifactorial stimulation of smooth muscle cell proliferation. The aim of this study was to investigate the in vitro effect of five potential antiproliferative agents on smooth muscle cells from human atherosclerotic femoral arteries.
Primary stenosing plaque material of 24 patients (aged 63 +/- 14 years) and restenosing plaque material of 7 patients (aged 65 +/- 9 years) was selectively extracted from femoral arteries by the Simpson atherectomy device. Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells by positive reaction with smooth muscle alpha-actin. Dalteparin sodium (0.001-100 anti-Xa units/ml), cyclosporine A (0.005-500 micrograms/ml), colchicine (0.00004-4 pg/ml), etoposide (0.002-200 micrograms/ml), and doxorubicin (0.0005-50 micrograms/ml) were added to the cultures. Six days after seeding, cells were trypsinized and cell number was measured by a cell counter. All five agents tested exhibited a significant inhibition of smooth muscle cell proliferation (P < 0.001). After an incubation time of 48 h, the cytoskeletal components, alpha-actin, vimentin, and microtubules were investigated. At peak concentrations, all five tested agents except dalteparin sodium caused severe damage to the cytoskeleton.
All five potential antiproliferative agents exhibited a significant inhibition of smooth muscle cell proliferation. The development of new intravascular delivery systems may open the way for local antiproliferative treatment strategies in interventional cardiology.
对再狭窄生物学认识的最新进展表明，其主要由平滑肌细胞增殖的多因素刺激引起。本研究的目的是调查五种潜在抗增殖剂对人动脉粥样硬化股动脉平滑肌细胞的体外作用。
通过Simpson旋切装置从股动脉中选择性提取24例患者（年龄63±14岁）的原发性狭窄斑块材料和7例患者（年龄65±9岁）的再狭窄斑块材料。通过酶解分离细胞，并通过与平滑肌α-肌动蛋白的阳性反应鉴定为平滑肌细胞。将达肝素钠（0.001 - 100抗Xa单位/毫升）、环孢素A（0.005 - 500微克/毫升）、秋水仙碱（0.00004 - 4皮克/毫升）、依托泊苷（0.002 - 200微克/毫升）和阿霉素（0.0005 - 50微克/毫升）添加到培养物中。接种6天后，用胰蛋白酶消化细胞，并用细胞计数器测量细胞数量。所有五种测试药物均表现出对平滑肌细胞增殖的显著抑制作用（P < 0.001）。孵育48小时后，研究细胞骨架成分α-肌动蛋白、波形蛋白和微管。在峰值浓度下，除达肝素钠外的所有五种测试药物均对细胞骨架造成严重损伤。
所有五种潜在抗增殖剂均表现出对平滑肌细胞增殖的显著抑制作用。新型血管内给药系统的开发可能为介入心脏病学中的局部抗增殖治疗策略开辟道路。
