{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:21:58Z","timestamp":1772252518884,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,28]],"date-time":"2021-11-28T00:00:00Z","timestamp":1638057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP21K08037"],"award-info":[{"award-number":["JP21K08037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells10123344","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T01:49:58Z","timestamp":1638150598000},"page":"3344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Repeated Social Defeat Exaggerates Fibrin-Rich Clot Formation by Enhancing Neutrophil Extracellular Trap Formation via Platelet\u2013Neutrophil Interactions"],"prefix":"10.3390","volume":"10","author":[{"given":"Takeshi","family":"Sugimoto","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6532-6808","authenticated-orcid":false,"given":"Hiroyuki","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naotoshi","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichiro","family":"Motoyama","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Saburi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Miyawaki","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriyuki","family":"Wakana","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Kami","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-4303","authenticated-orcid":false,"given":"Takehiro","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masakazu","family":"Ibi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kinjo Gakuin University, Nagoya 463-8521, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoaki","family":"Matoba","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1001\/jamapsychiatry.2014.2502","article-title":"Mortality in mental disorders and global disease burden implications: A systematic review and meta-analysis","volume":"72","author":"Walker","year":"2015","journal-title":"JAMA Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1093\/eurheartj\/eht462","article-title":"Depression and cardiovascular disease: A clinical review","volume":"35","author":"Hare","year":"2014","journal-title":"Eur. 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