MIGRATION OF SMOOTH-MUSCLE AND ENDOTHELIAL-CELLS - CRITICAL EVENTS IN RESTENOSIS
MIGRATION OF SMOOTH-MUSCLE AND ENDOTHELIAL-CELLS - CRITICAL EVENTS IN RESTENOSIS
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DOI：
10.1161/01.cir.86.3.723
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发表时间：
1992-09-01
期刊：
影响因子：
37.8
通讯作者：
CASSCELLS, W
中科院分区：
文献类型：
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作者：
CASSCELLS, W
经皮冠状动脉腔内成形术（PTCA）后的再狭窄仍然是一个挑战。多种治疗，包括抗血小板和抗凝剂、钙拮抗剂和血管紧张素转换酶抑制剂、皮质类固醇、血管内假体、斑块切除术、鱼油饮食和许多其他治疗，对再狭窄的发生率只有适度的影响。12这些结果突出了我们对潜在机制所知甚少。呼吸暂停的病理学大多数报告表明，早期再狭窄--PTCA后数小时至数天--是由于血栓形成，弹性回缩和血管痉挛也有一定的作用。3，4相反，晚期再狭窄的组织学结构5 -8主要是纤维细胞增殖，细胞外基质范围从松散的胶原纤维和蛋白多糖到致密的胶原瘢痕，在大多数情况下几乎没有炎性细胞和脂质。新鲜血栓在大多数标本中是次要成分，但在许多情况下，经历透明化变化或被平滑肌细胞和巨噬细胞定植的未溶解凝块可能是重要成分。通过光学显微镜，大多数细胞具有间充质外观，类似于成纤维细胞。电子显微镜显示了多种表型。有些有大量的肌丝束和基底膜，表明平滑肌细胞（SMC）的起源。这是支持的存在下，α，-平滑肌肌动蛋白和波形蛋白，而不是结蛋白的免疫反应性。5 '7其他细胞缺乏这些特征，可能表现为与球囊损伤大鼠中增殖、迁移、基质分泌、新生内膜细胞相似的去分化SMC表型，如下所述。9，'0该组织学图像不同于稳定的动脉粥样硬化病变。后者，虽然在外观上有所不同，但通常显示更致密的瘢痕，更多的泡沫细胞，坏死碎片和胆固醇裂缝，
R estenosis after percutaneous transluminal coronary angioplasty (PTCA) continues to present a challenge. Multiple therapies, including an-tiplatelet and anticoagulant agents, calcium antagonists and inhibitors of angiotensin converting enzyme, corti-costeroids, endovascular prostheses, atherectomy, fish oil diets, and many other treatments have had only modest effects on the incidence of restenosis. 12 These results highlight how little we know of the underlying mechanisms.Pathology ofRestenosis Most reports indicate that early restenosis-hours to days after PTCA-is due to thrombosis, with some contribution by elastic recoil and vasospasm. 3, 4 In contrast, the histology of late restenosis5-8 is mainly fibrocellular proliferation with an extracellular matrix rang-ing from loose collagen fibrils and proteoglycans to dense collagen scar, with few inflammatory cells and little lipid in most cases. Fresh thrombus represents a minor component in the majority of specimens, but unlysed clot that has undergone hyaline change or been colonized by smooth muscle cells and macrophages is probably an important constituent in many cases. By light microscopy, most of the cells have a mesenchymal appearance, similar to that of fibroblasts. Electron microscopy reveals a variety of phenotypes. Some have substantial myofilament bundles and a basement membrane suggesting a smooth muscle cell (SMC) origin. This is supported by the presence of immunoreactivity for a,-smooth muscle actin and for vimentin and not desmin. 5'7 Other cells lack these features and may represent a more dedifferentiated SMC phenotype sim-ilar to the proliferating, migrating, matrix-secreting, neointimal cells in the balloon-injured rat, described below. 9,'0 This histological picture differs from that of stable atherosclerotic lesions. The latter, though variablein appearance, generally reveal more dense scar, more foam cells, necrotic debris and cholesterol clefts, old