传统的铂金属植入物可引起动脉粥样硬化而非健康动脉的再狭窄反应

Decis. Sci. Pub Date : 2023-06-19 DOI:10.3390/sci5020025
Lea M. Morath, Roger J. Guillory, A. A. Oliver, S. Q. Liu, Martin L. Bocks, G. Levy, J. Drelich, J. Goldman
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引用次数: 0

摘要

含铂支架通常用于高胆固醇血症患者,然而临床前支架评估通常在健康动物模型中进行,提供的关于高胆固醇血症条件下支架性能的信息不足。在这项研究中,我们使用ApoE - / -小鼠模型来测试高胆固醇血症对含铂植入物新内膜形成的影响。我们将直径125 μm的铂丝植入ApoE−/−和ApoE+/+小鼠腹主动脉6个月,然后对新内膜的大小和组成进行组织学和免疫荧光检测。结果发现,与ApoE+/+小鼠相比,ApoE−/−小鼠形成的新内膜面积大4倍,厚度大10倍。与ApoE+/+相比,ApoE−/−小鼠中形成的新内膜含有更多的脂质,其覆盖范围是ApoE+/+的370倍,SMCs增加了3倍,巨噬细胞增加了22倍。两个小鼠品系均再生了合流内皮。ApoE−/−小鼠经历的管腔减少更接近于人类临床相关的再狭窄。总的来说,对铂动脉植入物的反应高度依赖于动脉粥样硬化环境。
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Conventional Platinum Metal Implants Provoke Restenosis Responses in Atherogenic but Not Healthy Arteries
Platinum-containing stents are commonly used in humans with hypercholesterolemia, whereas preclinical stent evaluation has commonly been performed in healthy animal models, providing inadequate information about stent performance under hypercholesterolemic conditions. In this investigation, we used an ApoE−/− mouse model to test the impact of hypercholesterolemia on neointima formation on platinum-containing implants. We implanted 125 μm diameter platinum wires into the abdominal aortas of ApoE−/− and ApoE+/+ mice for 6 months, followed by histological and immunofluorescence examination of neointimal size and composition. It was found that ApoE−/− mice developed neointimas with four times larger area and ten times greater thickness than ApoE+/+ counterparts. Neointimas developed in the ApoE−/− mice also contained higher amounts of lipids quantified as having 370 times more coverage compared to ApoE+/+, a 3-fold increase in SMCs, and a 22-fold increase in macrophages. A confluent endothelium had regenerated in both mouse strains. The ApoE−/− mice experienced luminal reductions more closely resembling clinically relevant restenosis in humans. Overall, the response to platinum arterial implants was highly dependent upon the atherogenic environment.
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