کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5685120 | 1597932 | 2016 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of coagulation proteases Xa and IIa decreases ischemia-reperfusion injuries in a preclinical renal transplantation model
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کلمات کلیدی
α-SMAMMP-2MCP-1iNOSPAI-1ICAM-1GAPDHTGF-βDCDFBSUFHVCAM-1HES - او هستα-smooth muscle actin - اکتین عضله آلفا صافischemia–reperfusion - ایسکمی-رپرفیوژنHAEC - اینinterleukin - اینترلوکینTAT - تاتTransforming growth factor β - تبدیل فاکتور رشد βPar - توسطtumor necrosis factor alpha - تومور نکروز عامل آلفاEMT - تکنسین فوریتهای پزشکیUniversity of Wisconsin - دانشگاه ویسکانسینfetal bovine serum - سرم جنین گاوhuman aortic endothelial cell - سلول اندوتلیال آئورت انسانinducible nitric oxide synthase - سنتاز اکسید نیتریک القاییTissue factor - عامل بافتIris - عنبیهTNF-α - فاکتور نکروز توموری آلفاmatrix metalloproteinase 2 - ماتریکس متالوپروتئیناز 2Intercellular adhesion molecule 1 - مولکول چسبندگی بین سلولی 1Vascular cell adhesion molecule 1 - مولکول چسبندگی سلولی عروقی 1NEP - نپunfractionated heparin - هپارین غیر اشباع شدهmonocyte chemoattractant protein 1 - پروتئین cheoattractant monocyte 1plasminogen activator inhibitor type-1 - پلاسمینوژن فعال کننده مهار کننده نوع 1Epithelial–mesenchymal transition - گذار اپیتلیال-مزانشیمیglyceraldehyde 3-phosphate dehydrogenase - گلیسرولیدید 3-فسفات دهیدروژنازprotease-activated receptor - گیرنده پروتئاز فعال
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
پزشکی و دندانپزشکی (عمومی)
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Inhibition of coagulation proteases Xa and IIa decreases ischemia-reperfusion injuries in a preclinical renal transplantation model Inhibition of coagulation proteases Xa and IIa decreases ischemia-reperfusion injuries in a preclinical renal transplantation model](/preview/png/5685120.png)
چکیده انگلیسی
Coagulation is an important pathway in the pathophysiology of ischemia-reperfusion injuries. In particular, deceased after circulatory death (DCD) donors undergo a no-flow period, a strong activator of coagulation. Hence, therapies influencing the coagulation cascade must be developed. We evaluated the effect of a new highly specific and effective anti-Xa/IIa molecule, with an integrated innovative antidote site (EP217609), in a porcine preclinical model mimicking injuries observed in DCD donor kidney transplantation. Kidneys were clamped for 60 minutes (warm ischemia), then flushed and preserved for 24 hours at 4°C in University of Wisconsin (UW) solution (supplemented or not). EP217609-supplemented UW solution (UW-EP), compared with unfractionated heparin-supplemented UW solution (UW-UFH) or UW alone (UW). A mechanistic investigation was conducted in vitro: addition of EP217609 to endothelial cells during hypoxia at 4°C in the UW solution inhibited thrombin generation during reoxygenation at 37°C in human plasma and reduced tumor necrosis factor alpha, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 messenger RNA cell expressions. In vivo, function recovery was markedly improved in the UW-EP group. Interestingly, levels of thrombin-antithrombin complexes (reflecting thrombin generation) were reduced 60 minutes after reperfusion in the UW-EP group. In addition, 3 months after transplantation, lower fibrosis, epithelial-mesenchymal transition, inflammation, and leukocyte infiltration were observed. Using this new dual anticoagulant, anti-Xa/IIa activity during kidney flush and preservation is protected by reducing thrombin generation at revascularization, improving early function recovery, and decreasing chronic lesions. Such an easy-to-deploy clinical strategy could improve marginal graft outcome.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Translational Research - Volume 178, December 2016, Pages 95-106.e1
Journal: Translational Research - Volume 178, December 2016, Pages 95-106.e1
نویسندگان
Solenne Tillet, Sébastien Giraud, Thomas Kerforne, Thibaut Saint-Yves, Sandrine Joffrion, Jean-Michel Goujon, Jerôme Cau, Gérard Mauco, Maurice Petitou, Thierry Hauet,