Stroke最新文献 - Book学术

Inhibiting Monocyte Migration Reduces Arterial Thrombosis and Facilitates Thrombolysis. 抑制单核细胞迁移可减少动脉血栓形成并促进溶栓。

IF 8.9 1区医学

Stroke Pub Date : 2025-10-10 DOI: 10.1161/STROKEAHA.125.052352

Hee Jeong Jang, Jiwon Kim, Ha Kim, Taesu Kim, Jinyong Chung, Sebastian Cremer, Marvin Krohn-Grimberghe, Eo-Jin Kim, Dawid Schellingerhout, Matthias Nahrendorf, Dong-Eog Kim

{"title":"Inhibiting Monocyte Migration Reduces Arterial Thrombosis and Facilitates Thrombolysis.","authors":"Hee Jeong Jang, Jiwon Kim, Ha Kim, Taesu Kim, Jinyong Chung, Sebastian Cremer, Marvin Krohn-Grimberghe, Eo-Jin Kim, Dawid Schellingerhout, Matthias Nahrendorf, Dong-Eog Kim","doi":"10.1161/STROKEAHA.125.052352","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.052352","url":null,"abstract":"Background: Monocytes contribute to the initiation and propagation of venous thrombosis. Little is known about the roles monocytes play in arterial thrombosis, the cause of stroke and myocardial infarction.Methods: We investigated how CCR2 (chemokine receptor 2) knockout (-/-)-mediated monocyte deficiency affects platelet function, blood coagulation, thrombus volume, and thrombolytic susceptibility in 666 male mice with FeCl3-mediated carotid arterial thrombosis, including 365 C57BL/6 wild type (WT) mice, 295 CCR2-/- mice, and 6 CX3CR1-GFP (CX3C chemokine receptor 1-green fluorescent protein) mice.Results: Intravital microscopy and flow cytometry showed that both neutrophils and monocytes were recruited to the acute arterial thrombus, as observed 30 minutes postthrombosis. Platelet function tests demonstrated platelet aggregation to be lower in the whole blood of CCR2-/- mice (versus C57BL/6 WT mice) but not in their leukocyte-free platelet-rich plasma, suggesting this platelet dysfunction is cell-mediated. Flow cytometry experiments revealed lower numbers of monocyte-platelet aggregates in the blood of CCR2-/- mice, compared with C57BL/6 WT mice. Blood levels of FXIII (factor XIII) and monocyte levels of FXIII-A were increased after carotid thrombosis in C57BL/6 WT mice but not CCR2-/- mice. Further, in vivo micro-computed tomography-based thrombus imaging using fibrin-targeted gold nanoparticles and histology showed that CCR2-/- mice had smaller thrombi (0.112±0.002 mm3, n=22) than C57BL/6 WT mice (0.125±0.007 mm3, n=27; P<0.01), with increased porosity and reduced fibrin cross-linking. Moreover, tPA (tissue-type plasminogen activator) mediated thrombus volume reduction progressed up to ≈1 hour faster during the initial 3-hour period in CCR2-/- mice and CCR2-siRNA-treated mice, compared with C57BL/6 WT mice. In addition, clopidogrel reduced baseline thrombus volume more, but CCR2-/- better facilitated tPA-mediated thrombolysis.Conclusions: CCR2 antagonism decreases platelet aggregation and reduces FXIII (factor XIII) levels in blood and monocytes, thus driving arterial thrombosis towards the generation of a relatively small, porous, more lysable clot.","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}