...
首页> 外文期刊>Journal of thrombosis and haemostasis: JTH >Recombinant soluble apyrase APT102 inhibits thrombosis and intimal hyperplasia in vein grafts without adversely affecting hemostasis or re-endothelialization
【24h】

Recombinant soluble apyrase APT102 inhibits thrombosis and intimal hyperplasia in vein grafts without adversely affecting hemostasis or re-endothelialization

机译:重组可溶性戊酶APT102抑制静脉移植物中的血栓形成和内膜增生,而不会对止血或重新内皮化产生不利影响

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       

摘要

Background: Occlusion of vein grafts (VGs) after bypass surgery, owing to thrombosis and intimal hyperplasia (IH), is a major clinical problem. Apyrases are enzymes that scavenge extracellular ATP and ADP, and promote adenosine formation at sites of vascular injury, and hence have the potential to inhibit VG pathology. Objectives: To examine the effects of recombinant soluble human apyrase, APT102, on platelets, smooth muscle cells (SMCs) and endothelial cells (ECs) in vitro, and on thrombosis and IH in murine VGs. Methods: SMC and EC proliferation and migration were studied in vitro. Inferior vena cava segments from donor mice were grafted into carotid arteries of recipient mice. Results: APT102 potently inhibited ADP-induced platelet aggregation and VG thrombosis, but it did not impair surgical hemostasis. APT102 did not directly inhibit SMC or EC proliferation, but significantly attenuated the effects of ATP on SMC and EC proliferation. APT102 significantly inhibited SMC migration, but did not inhibit EC migration, which may be mediated, at least in part, by inhibition of SMC, but not EC, migration by adenosine. At 4 weeks after surgery, there was significantly less IH in VGs of APT102-treated mice than in control VGs. APT102 significantly inhibited cell proliferation in VGs, but did not inhibit re-endothelialization. Conclusions: Systemic administration of a recombinant human apyrase inhibits thrombosis and IH in VGs without increasing bleeding or compromising re-endothelialization. These results suggest that APT102 has the potential to become a novel, single-drug treatment strategy to prevent multiple pathologic processes that drive early adverse remodeling and occlusion of VGs.
机译:背景:由于血栓形成和内膜增生(IH),静脉移植物(VGS)闭塞静脉移植(VGS)是一个主要的临床问题。亚替酶是清除细胞外ATP和ADP的酶,并促进血管损伤部位的腺苷形成,因此有可能抑制VG病理学。目的:在体外检查重组可溶性人屏幕,APT102,平滑肌细胞(SMC)和内皮细胞(ECS)的影响,以及鼠脉型中的血栓形成和IH。方法:在体外研究SMC和EC增殖和迁移。将供体小鼠的较差的腔静脉段移植到受体小鼠的颈动脉中。结果:APT102有效地抑制ADP诱导的血小板聚集和VG血栓形成,但它没有损害手术止血。 APT102没有直接抑制SMC或EC增殖,但显着减弱了ATP对SMC和EC增殖的影响。 APT102显着抑制SMC迁移,但没有抑制EC迁移,其可以至少部分地通过抑制SMC来介导,但不是EC,由腺苷迁移。在手术后4周,APT102处理小鼠的VGS显着较少的IH,而不是对照VGS。 APT102在VGS中显着抑制细胞增殖,但没有抑制重新内皮化。结论:重组人屏幕的全身施用抑制VGS中的血栓形成和IH,而不会增加出血或损害重新内皮化。这些结果表明,APT102具有成为一种新的单药处理策略,以防止多种病理过程推动早期不利重塑和VGS闭塞的病理过程。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号