Repeated Social Defeat Exaggerates Fibrin-Rich Clot Formation by Enhancing Neutrophil Extracellular Trap Formation via Platelet-Neutrophil Interactions.
Repeated Social Defeat Exaggerates Fibrin-Rich Clot Formation by Enhancing Neutrophil Extracellular Trap Formation via Platelet-Neutrophil Interactions.
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DOI：
10.3390/cells10123344
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发表时间：
2021-11-28
期刊：
影响因子：
6
通讯作者：
Matoba S
中科院分区：
文献类型：
--
作者：
Sugimoto T;Yamada H;Wada N;Motoyama S;Saburi M;Kubota H;Miyawaki D;Wakana N;Kami D;Ogata T;Ibi M;Matoba S
抑郁症是心血管疾病（CVD）的独立危险因素。我们以前已经表明，反复的社会失败（RSD）通过增强中性粒细胞胞外陷阱（NET）的形成来夸大动脉粥样硬化的发展。在这项研究中，我们研究了RSD对动脉血栓形成的影响。通过将8周龄雄性野生型小鼠（C57 BL/6 J）与较大的CD-1小鼠一起圈养在共用的饲养笼中，使其暴露于RSD。他们连续10天每天都受到剧烈的身体接触。在确认抑郁样行为后，小鼠经历FeCl 3诱导的颈动脉损伤，并在3小时后进行分析。虽然两组之间的血栓体积相当，但在失败的小鼠中纤维蛋白（原）阳性区域显著增加，其中Ly-6 G阳性细胞与Cit-H3阳性染色明显共定位。用DNase I治疗完全减少了失败小鼠中过度的富含纤维蛋白的凝块形成。流式细胞术分析表明，中性粒细胞CD 11b的表达前FeCl 3应用显着高于在对照组小鼠在失败的小鼠。在体外NET的形成诱导的活化血小板显着增加失败的小鼠，这是基本上抑制抗CD 11b抗体治疗。我们的研究结果表明，RSD通过促进NET的形成来促进动脉损伤后富含纤维蛋白的凝块的形成，这表明NET可以成为抑郁症相关CVD的新治疗靶点。
Depression is an independent risk factor for cardiovascular disease (CVD). We have previously shown that repeated social defeat (RSD) exaggerates atherosclerosis development by enhancing neutrophil extracellular trap (NET) formation. In this study, we investigated the impact of RSD on arterial thrombosis. Eight-week-old male wild-type mice (C57BL/6J) were exposed to RSD by housing with larger CD-1 mice in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days. After confirming depression-like behaviors, mice underwent FeCl3-induced carotid arterial injury and were analyzed after 3 h. Although the volume of thrombi was comparable between the two groups, fibrin(ogen)-positive areas were significantly increased in defeated mice, in which Ly-6G-positive cells were appreciably co-localized with Cit-H3-positive staining. Treatment with DNase I completely diminished exaggerated fibrin-rich clot formation in defeated mice. Flow cytometric analysis showed that neutrophil CD11b expression before FeCl3 application was significantly higher in defeated mice than in control mice. In vitro NET formation induced by activated platelets was significantly augmented in defeated mice, which was substantially inhibited by anti-CD11b antibody treatment. Our findings demonstrate that RSD enhances fibrin-rich clot formation after arterial injury by enhancing NET formation, suggesting that NET can be a new therapeutic target in depression-related CVD.
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影响因子：
3.3
作者：
Felger JC;Lotrich FE
通讯作者：
Lotrich FE
影响因子：
82.9
作者：
通讯作者：
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影响因子：
32.4
作者：
Adrover, Jose M.;del Fresno, Carlos;Hidalgo, Andres
通讯作者：
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抑郁和心血管疾病：血小板的观点。
影响因子：
5.6
作者：
Amadio P;Zarà M;Sandrini L;Ieraci A;Barbieri SS
通讯作者：
Barbieri SS
影响因子：
3.6
作者：
Lisman T
通讯作者：
Lisman T