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比较包被有抗 CD34 抗体和血管内皮钙黏蛋白抗体的支架的内皮化和新生内膜形成。

Comparison of endothelialization and neointimal formation with stents coated with antibodies against CD34 and vascular endothelial-cadherin.

机构信息

Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Republic of Korea.

出版信息

Biomaterials. 2012 Dec;33(35):8917-27. doi: 10.1016/j.biomaterials.2012.08.066. Epub 2012 Sep 14.

Abstract

Vascular endothelial-cadherin (VE-cadherin) is exclusively expressed on the late endothelial progenitor cells (EPC). Therefore, VE-cadherin could be an ideal target surface molecule to capture circulating late EPC. In the present study, we evaluated whether anti-VE-cadherin antibody-coated stents (VE-cad stents) might accelerate endothelial recovery and reduce neointimal formation more than anti-CD34 antibody-coated stents (CD34 stents) through the superior ability to capture the late EPC. The stainless steel stents were coated with anti-human VE-cadherin antibodies or anti-human CD34 antibodies under the same condition. In vitro, VE-cad stents showed higher number of adhering EPC (823.6 ± 182.2 versus 379.2 ± 137.2 cells per HPF, p < 0.001). VE-cad stents also demonstrated better specific capturing of cells with endothelial lineage markers than CD34 stents did in flow cytometric analysis. VE-cad stents showed more effective re-endothelialization after 1 h, 24 h, and 3 days in vivo. At 42 days, VE-cad stents demonstrated significantly smaller neointima area (0.92 ± 0.38 versus 1.24 ± 0.41 mm(2), p = 0.002) and significantly lower PCNA positive cells in neointima (1684.8 ± 658.8/mm(2) versus 2681.7 ± 375.1/mm(2), p = 0.008), compared with CD34 stents. In conclusion, VE-cad stents captured EPC and endothelial cells more selectively in vitro, accelerated re-endothelialization over stents, and reduced neointimal formation in vivo, compared with CD34 stents.

摘要

血管内皮钙黏蛋白(VE-cadherin)仅在上皮祖细胞(EPC)晚期表达。因此,VE-cadherin 可能成为捕获循环晚期 EPC 的理想靶表面分子。在本研究中,我们通过评价抗 VE-cadherin 抗体涂层支架(VE-cad 支架)是否具有优于抗 CD34 抗体涂层支架(CD34 支架)的捕获晚期 EPC 的能力,从而更能加速内皮修复并减少新生内膜形成。将不锈钢支架用抗人 VE-cadherin 抗体或抗人 CD34 抗体在相同条件下进行涂层。在体外,VE-cad 支架显示出更多黏附的 EPC(823.6 ± 182.2 个/HPF 与 379.2 ± 137.2 个/HPF,p < 0.001)。与 CD34 支架相比,流式细胞术分析显示 VE-cad 支架对内皮谱系标志物的细胞具有更好的特异性捕获。在体内,支架在 1 h、24 h 和 3 d 后表现出更有效的再内皮化。在 42 天,VE-cad 支架显示出更小的新生内膜面积(0.92 ± 0.38 mm²与 1.24 ± 0.41 mm²,p = 0.002)和新生内膜中 PCNA 阳性细胞更少(1684.8 ± 658.8/mm²与 2681.7 ± 375.1/mm²,p = 0.008),与 CD34 支架相比。总之,与 CD34 支架相比,VE-cad 支架在体外更能选择性地捕获 EPC 和内皮细胞,在体内更能加速再内皮化,并减少新生内膜形成。

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