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替罗非班积极调节β1 整合素,并有利于内皮细胞在聚乳酸生物聚合物血管支架(BVS)上的生长。

Tirofiban Positively Regulates β1 Integrin and Favours Endothelial Cell Growth on Polylactic Acid Biopolymer Vascular Scaffold (BVS).

机构信息

Unità Operativa di Interventistica Cardiovascolare, Presidio Ospedaliero Pineta Grande, Castel Volturno, Italy.

Unità Operativa di Emodinamica, Casa di Salute Santa Lucia, San Giuseppe Vesuviano, Naples, Italy.

出版信息

J Cardiovasc Transl Res. 2018 Jun;11(3):201-209. doi: 10.1007/s12265-018-9805-1. Epub 2018 Apr 25.

DOI:10.1007/s12265-018-9805-1
PMID:29696533
Abstract

An unexpectedly high incidence of thrombosis in patients that received the polylactic acid bioresorbable vascular scaffold (BVS) suggests a delayed/incomplete endothelial repair with this stent. The anti-platelet agent tirofiban stimulates endothelial cell migration and proliferation, mediated by VEGF production. We investigated the tirofiban effect on the migration and adhesion of endothelial cells to BVS, in vitro. We performed human umbilical endothelial cell (HUVEC) cultures in the presence of BVS. Tirofiban, similarly to VEGF, increased the ability of HUVEC to grow on the vascular scaffold, compared to unstimulated or abciximab-treated cells. Tirofiban increased HUVEC expression of β1 and β3 integrins along with collagen and fibronectin. A role for β1 integrin in the "pro-adhesive and -migratory" signals elicited by tirofiban was suggested by use of an anti-β1-blocking antibody that prevented poly-levo-lactic acid vascular scaffold colonization. Our study suggests that tirofiban may improve the outcomes of patients receiving BVS by accelerating stent endothelization.

摘要

在接受聚乳酸可吸收血管支架(BVS)治疗的患者中,血栓形成的发生率出乎意料地高,这表明这种支架存在内皮修复延迟/不完全的情况。抗血小板药物替罗非班通过促进血管内皮生长因子(VEGF)的产生来刺激内皮细胞的迁移和增殖。我们研究了替罗非班对体外内皮细胞向 BVS 的迁移和黏附的影响。我们在存在 BVS 的情况下进行了人脐静脉内皮细胞(HUVEC)培养。与未刺激或阿昔单抗处理的细胞相比,替罗非班增加了 HUVEC 在血管支架上生长的能力,类似于 VEGF 的作用。替罗非班增加了 HUVEC 表达β1 和β3 整合素以及胶原蛋白和纤维连接蛋白。通过使用抗β1 阻断抗体,该抗体阻止了聚左旋乳酸血管支架的定植,提示β1 整合素在替罗非班引发的“促黏附和促迁移”信号中起作用。我们的研究表明,替罗非班通过加速支架内皮化,可能改善接受 BVS 治疗的患者的预后。

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本文引用的文献

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Endoglin moves and shapes endothelial cells.内皮糖蛋白使内皮细胞移动和塑形。
Nat Cell Biol. 2017 May 31;19(6):593-595. doi: 10.1038/ncb3543.
2
Endoglin prevents vascular malformation by regulating flow-induced cell migration and specification through VEGFR2 signalling.内皮糖蛋白通过VEGFR2信号通路调节血流诱导的细胞迁移和分化,从而预防血管畸形。
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Late neoatherosclerotic scaffold failure: An unexpected achilles heel for current bioresorbable scaffold technology?
晚期新生动脉粥样硬化性支架失败:当前生物可吸收支架技术意想不到的致命弱点?
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Re-Endothelialization Study on Endovascular Stents Seeded by Endothelial Cells through Up- or Downregulation of VEGF.通过上调或下调血管内皮生长因子(VEGF),对内皮细胞接种的血管内支架进行再内皮化研究。
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Bioresorbable scaffolds: a new paradigm in percutaneous coronary intervention.生物可吸收支架:经皮冠状动脉介入治疗的新范例。
BMC Cardiovasc Disord. 2016 Feb 12;16:38. doi: 10.1186/s12872-016-0207-5.
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Endoglin regulates mural cell adhesion in the circulatory system.内皮糖蛋白调节循环系统中的壁细胞黏附。
Cell Mol Life Sci. 2016 Apr;73(8):1715-39. doi: 10.1007/s00018-015-2099-4. Epub 2015 Dec 8.
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Very Late Scaffold Thrombosis: Intracoronary Imaging and Histopathological and Spectroscopic Findings.极晚期支架血栓:冠状动脉内影像学及组织病理学和光谱学研究结果。
J Am Coll Cardiol. 2015 Oct 27;66(17):1901-14. doi: 10.1016/j.jacc.2015.08.853.
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Vascul Pharmacol. 2014 May-Jun;61(2-3):63-71. doi: 10.1016/j.vph.2014.04.002. Epub 2014 Apr 18.