Copper-induced inflammatory reactions of rat carotid arteries mimic restenosis/arteriosclerosis-like neointima formation
Copper-induced inflammatory reactions of rat carotid arteries mimic restenosis/arteriosclerosis-like neointima formation
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DOI：
10.1016/s0021-9150(96)06039-x
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发表时间：
1997-04-01
期刊：
影响因子：
5.3
通讯作者：
Buddecke, E
中科院分区：
文献类型：
--
作者：
Volker, W;Dorszewski, A;Buddecke, E
血管成形术后动脉硬化和再狭窄的发病机制与动脉组织的炎症和纤维增生反应有关。我们通过在大鼠颈动脉周围植入硅铜袖套来诱导非感染性炎症。从氧化铜中释放的铜离子引发并模仿血管成形术后血管再狭窄和动脉硬化病变的所有形态学特征。采用电子显微镜、光镜、免疫组织化学等方法对铜致病变进行分析，并用形态计量学进行定量分析。在铜诱导的组织反应的第一阶段（3天），巨噬细胞和多形核白细胞通过内皮侵入，在内皮下空间积聚，引发平滑肌细胞增殖，平滑肌细胞从中膜通过内弹性层迁移到内膜。3周内，积聚的平滑肌细胞、巨噬细胞、白细胞和新合成的细胞外基质形成圆形、多偏心的纤维化增厚，使血管管腔变窄30-40%。在第20天至第43天，11只动物中有3只的内层结构破坏导致局灶性破裂和动脉瘤样血管壁扩张。随着时间的推移，新生内膜的厚度逐渐增加，导致相应的血管管腔缩小。对照组和无铜硅袖口组动物颈动脉未见异常病理表现。我们的研究结果表明，炎症诱导剂可以促进和模拟再狭窄和动脉硬化样病变，铜袖带模型可能有助于探索新的干预方法。(C) 1997爱思唯尔科学爱尔兰有限公司
The pathogenesis of arteriosclerosis and of restenosis after angioplasty is linked with an inflammatory and fibroproliferative response of the arterial tissue. We have induced a non-infectious inflammation by implanting a silicon-copper cuff around rat carotid arteries. The copper ions released from the oxidized copper initiate and mimic all morphological features of post-angioplasty restenotic and arteriosclerotic lesions. The copper-induced lesions were analyzed by electron and light microscopy, immunohistochemical methods and quantified by morphometry. During the first phase of copper-induced tissue reaction (3 days), macrophages and polymorphonuclear leucocytes invaded through the endothelium, accumulated in the subendothelial space and triggered the proliferation of smooth muscle cells which then migrated from the tunica media through the lamina elastica interna into the intima. Within 3 weeks, the accumulated smooth muscle cells, macrophages, leucocytes and newly synthesized extracellular matrix formed a circular mostly eccentric fibrotic thickening that narrows the vessel lumen by 30-40%. The accompanying structural disorganization of the medial layer led to focal rupture and aneurysm-like dilatation of the vessel wall in 3 of 11 animals between day 20 and 43. The neointima progressively increased in thickness over time leading to corresponding reduction of the vessel lumen. The carotid arteries of control animals and animals treated with copper-free silicon cuffs showed no abnormal pathological appearence. Our results show that inflammation-inducing agents can contribute to and simulate restenosis- and arteriosclerosis-like lesions and that the copper-cuff model may be useful in the exploration of new approaches to intervention. (C) 1997 Elsevier Science Ireland Ltd.