Histological comparison of arterial thrombi in mice and men and the influence of Cl-amidine on thrombus formation.
Histological comparison of arterial thrombi in mice and men and the influence of Cl-amidine on thrombus formation.
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DOI：
10.1371/journal.pone.0190728
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Schulz C
中科院分区：
文献类型：
--
作者：
Novotny J;Chandraratne S;Weinberger T;Philippi V;Stark K;Ehrlich A;Pircher J;Konrad I;Oberdieck P;Titova A;Hoti Q;Schubert I;Legate KR;Urtz N;Lorenz M;Pelisek J;Massberg S;von Brühl ML;Schulz C
动脉血栓形成的药物治疗主要针对血小板和凝血因子，可导致出血并发症。目前正在动物身上研究针对免疫细胞和中性粒细胞胞外陷阱（NET）的新型抗血栓疗法。我们探讨了小鼠血栓形成模型中诱导的动脉血栓的免疫细胞组成是否与人类急性心肌梗死（AMI）患者相似。在一项针对 AMI 患者的前瞻性队列研究中，在经皮冠状动脉介入治疗期间采集了 81 个人类动脉血栓，并进行了详细的组织学分析。在小鼠中，使用两种不同的实验模型诱导动脉血栓：氯化铁 (FeCl3) 和颈动脉线损伤。我们发现，FeCl3 诱导的小鼠动脉血栓在免疫细胞组成方面与人类冠状动脉血栓高度一致，其中中性粒细胞是最丰富的细胞类型，并且存在 NET 和凝血因子。用蛋白质精氨酸脱亚胺酶 (PAD) 抑制剂 Cl-脒对小鼠进行药物治疗，可消除心肌梗塞模型中 NET 的形成，减少动脉血栓形成并限制损伤。中性粒细胞是急性心肌梗塞患者和动脉血栓形成小鼠模型中动脉血栓的标志。抑制 PAD 可能代表一种有趣的治疗动脉血栓形成的策略，以减少中性粒细胞相关的组织损伤并改善功能结果。
Medical treatment of arterial thrombosis is mainly directed against platelets and coagulation factors, and can lead to bleeding complications. Novel antithrombotic therapies targeting immune cells and neutrophil extracellular traps (NETs) are currently being investigated in animals. We addressed whether immune cell composition of arterial thrombi induced in mouse models of thrombosis resemble those of human patients with acute myocardial infarction (AMI). In a prospective cohort study of patients suffering from AMI, 81 human arterial thrombi were harvested during percutaneous coronary intervention and subjected to detailed histological analysis. In mice, arterial thrombi were induced using two distinct experimental models, ferric chloride (FeCl3) and wire injury of the carotid artery. We found that murine arterial thrombi induced by FeCl3 were highly concordant with human coronary thrombi regarding their immune cell composition, with neutrophils being the most abundant cell type, as well as the presence of NETs and coagulation factors. Pharmacological treatment of mice with the protein arginine deiminase (PAD)-inhibitor Cl-amidine abrogated NET formation, reduced arterial thrombosis and limited injury in a model of myocardial infarction. Neutrophils are a hallmark of arterial thrombi in patients suffering from acute myocardial infarction and in mouse models of arterial thrombosis. Inhibition of PAD could represent an interesting strategy for the treatment of arterial thrombosis to reduce neutrophil-associated tissue damage and improve functional outcome.
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影响因子：
27.4
作者：
Knight JS;Subramanian V;O'Dell AA;Yalavarthi S;Zhao W;Smith CK;Hodgin JB;Thompson PR;Kaplan MJ
通讯作者：
Kaplan MJ
影响因子：
6.7
作者：
Distelmaier, Klaus;Adlbrecht, Christopher;Kubicek, Markus
通讯作者：
Kubicek, Markus
影响因子：
20.3
作者：
Fay, WP;Parker, AC;Ginsburg, D
通讯作者：
Ginsburg, D
影响因子：
10.8
作者：
Ha, Tuanzhu;Hua, Fang;Li, Chuanfu
通讯作者：
Li, Chuanfu
影响因子：
20.3
作者：
Konings, Joke;Govers-Riemslag, Jose W. P.;Ariens, Robert A. S.
通讯作者：
Ariens, Robert A. S.