Voisard R, Dartsch P C, Seitzer U, Hannekum A, Roth D, Kochs M, Hombach V
Department of Cardiology, Angiology, Nephrology and Pneumology, University of Ulm, Germany.
Coron Artery Dis. 1993 Oct;4(10):935-42. doi: 10.1097/00019501-199310000-00014.
Restenosis after successful percutaneous transluminal coronary angioplasty remains the major clinical problem limiting the long-term efficacy of the treatment. Recent advances in the understanding of the biology of restenosis indicate that its cause is predominantly a multifactorial stimulation of smooth-muscle cell proliferation. The aim of this study was to investigate the in-vitro effect of antineoplastic agents on smooth-muscle cells isolated from human coronary plaque material.
Atherosclerotic tissue from coronary arteries was extracted from 15 patients of both sexes by thrombendarterectomy. Cells were isolated using enzymatic disaggregation and identified to be smooth-muscle cells with fluorescent antibodies for smooth-muscle-specific alpha-actin. The antineoplastic agents cytarabine (500-0.005 micrograms/ml), doxorubicin (50-0.0005 micrograms/ml), and vincristine (10-0.0001 micrograms/ml) were added to the cultures. Six days after seeding, the cells were trypsinized and then counted.
All three antineoplastic agents had a strong dose-dependent antiproliferative effect on cultured smooth-muscle cells. After the application of cytostatic agents, cells either became rounded or underwent complete lysis. Cytoskeletal elements, such as actin, microtubules, and vimentin, were largely altered.
This investigation examined the potential role of antineoplastic therapy in the prevention of restenosis after coronary angioplasty. The development of new intravascular delivery systems, such as coated stents, may open the way for local antiproliferative strategies in interventional cardiology.
经皮腔内冠状动脉成形术成功后再狭窄仍然是限制该治疗长期疗效的主要临床问题。对再狭窄生物学认识的最新进展表明，其原因主要是平滑肌细胞增殖的多因素刺激。本研究的目的是研究抗肿瘤药物对从人冠状动脉斑块材料中分离出的平滑肌细胞的体外作用。
通过血栓内膜切除术从15名男女患者的冠状动脉中提取动脉粥样硬化组织。使用酶解方法分离细胞，并用平滑肌特异性α-肌动蛋白的荧光抗体鉴定为平滑肌细胞。将抗肿瘤药物阿糖胞苷（500 - 0.005微克/毫升）、阿霉素（50 - 0.0005微克/毫升）和长春新碱（10 - 0.0001微克/毫升）加入培养物中。接种6天后，将细胞用胰蛋白酶消化，然后计数。
所有三种抗肿瘤药物对培养的平滑肌细胞均有强烈的剂量依赖性抗增殖作用。应用细胞抑制剂后，细胞要么变圆，要么完全裂解。细胞骨架成分，如肌动蛋白、微管和波形蛋白，发生了很大改变。
本研究探讨了抗肿瘤治疗在预防冠状动脉成形术后再狭窄中的潜在作用。新型血管内输送系统（如涂层支架）的开发可能为介入心脏病学中的局部抗增殖策略开辟道路。
