Aptamer BT200 对小鼠心肌缺血再灌注损伤具有保护作用。

IF 5.5 2区 医学 Q1 HEMATOLOGY Journal of Thrombosis and Haemostasis Pub Date : 2024-10-21 DOI:10.1016/j.jtha.2024.09.032
Xinyuan Chen, Xianying Liao, Guiping Lu, Yue Ma, Ruowen Wang, Ancai Yuan, Yuquan Xie, Jun Pu
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引用次数: 0

摘要

背景:心肌缺血再灌注(MI/R)损伤往往会影响心脏功能,导致患者预后不良,而目前还没有针对急性冠心病开发有效靶向药物的抗血管紧张素(VWF)合剂。然而,新开发的抗 VWF 合剂 BT200 不仅适用于脑卒中和血友病,还具有抗血栓形成的临床开发功能。BT200 在急性心肌梗死/急性心肌损伤中的作用尚不清楚:目的:在心肌梗死/急性心肌梗死的实验模型中研究适配体 BT200 的心脏保护作用:方法:对C57BL/6小鼠进行30分钟缺血和24小时再灌注,建立心肌缺血再灌注模型。小鼠接受静脉注射 cy3 标记的 BT200 治疗,并在不同时间点通过体内成像系统进行观察。然后,对小鼠进行取样,并通过超声心动图、Evans-TTC 染色、组织病理学、Western 印迹和实时 qPCR 检测来检测 24 小时再灌注后的心脏损伤和炎症反应:结果:BT200 合体能在 24 小时再灌注后进入并浸润缺血心肌。结果表明,BT200 能抑制 VWF A1 的活性并延长 MI/R 小鼠的出血时间。此外,经 BT200 治疗的小鼠梗死面积明显缩小,心肌梗死/再灌注后的心功能也有所改善。BT200 治疗还能缓解 MI/R 引起的微血管阻塞、炎症反应和心肌细胞凋亡:结论:用 BT200 药理学靶向 VWF 可减轻小鼠模型中的急性 MI/R 损伤,可能是急性心肌梗死的一种新型治疗策略。
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Aptamer BT200 is protective against myocardial ischemia-reperfusion injury in mice.

Background: Myocardial ischemia-reperfusion (MI/R) injury tends to affect cardiac function and leads to poor patient prognosis, and there is still no effectively targeted drug to develop anti-von Willebrand factor (VWF) aptamer in acute coronary heart disease. However, the newly anti-VWF aptamer BT200 is applied not only for stroke and hemophilia but also for antithrombolism function in clinical development. The role of BT200 in acute myocardial injury during MI/R is still unknown.

Objectives: To investigate the cardioprotective effect of aptamer BT200 in a mouse model of MI/R.

Methods: C57BL/6 mice were subjected to 30-minute ischemia and 24-hour reperfusion to establish MI/R model. Mice were treated with intravenous injection of cy3-labeled BT200 and were observed by an in vivo imaging system at different time points. Then, mice were sampled and evaluated by echocardiography, Evans triphenyltetrazolium chloride staining, histopathologic, western blotting, and real-time quantitative polymerase chain reaction assays to detect cardiac injury and inflammation response after 24-hour reperfusion.

Results: BT200 aptamer can enter and infiltrate into the ischemic myocardium after 24-hour reperfusion. BT200 was shown to inhibit VWF A1 activity and prolong bleeding time in MI/R mice. Moreover, BT200-treated mice had a significant reduction in infarct size and an improvement in cardiac function post-MI/R. BT200 treatment can also alleviate MI/R-induced microvascular obstruction, inflammation response, and cardiomyocyte apoptosis.

Conclusion: Pharmacologic targeting of VWF with BT200 alleviates acute MI/R injury in a murine model and may be a novel therapy strategy for acute myocardial infarction.

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来源期刊
Journal of Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis 医学-外周血管病
CiteScore
24.30
自引率
3.80%
发文量
321
审稿时长
1 months
期刊介绍: The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.
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