{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:16:13Z","timestamp":1790514973341,"version":"4.1.0"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              Deep vein thrombosis results from a combination of risk factors including genetic conditions, obesity, drugs, pregnancy, aging, and malignancy. We examined pathophysiological roles of the TNF-\u03b1 (tumor necrosis factor-\u03b1)\u2013TNF-Rp55 (tumor necrosis factor receptor p55) axis in thrombus resolution using\n              <jats:italic>Tnfrp5<\/jats:italic>\n              5\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (TNF-Rp55\u2013deficient) mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              On ligating the inferior vena cava of wild-type (WT) mice, venous thrombi formed and grew progressively until 5 days but shrunk to &lt;50% of the thrombus weight at day 14. Concomitantly, inferior vena cava ligation enhanced intrathrombotic gene expression of\n              <jats:italic>Tnfa<\/jats:italic>\n              and\n              <jats:italic>Tnfrp55<\/jats:italic>\n              , and intrathrombotic macrophages expressed both TNF-\u03b1 and TNF-Rp55 proteins. In\n              <jats:italic>Tnfrp5<\/jats:italic>\n              5\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice treated with the same manner, thrombus formed at a similar rate for 5 days, but shrinking was delayed compared with WT mice. Moreover, the blood flow recovery in thrombosed inferior vena cava was suspended in\n              <jats:italic>Tnfrp5<\/jats:italic>\n              5\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice compared with WT mice. Intrathrombotic\n              <jats:italic>Plau<\/jats:italic>\n              (urokinase-type plasminogen activator),\n              <jats:italic>Mmp2<\/jats:italic>\n              (matrix metalloproteinase 2), and\n              <jats:italic>Mmp9<\/jats:italic>\n              (matrix metalloproteinase 9) mRNA expression was significantly reduced in\n              <jats:italic>Tnfrp5<\/jats:italic>\n              5\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, compared with WT ones. Supportingly, the administration of anti\u2013TNF-\u03b1 antibody or TNF-\u03b1 inhibitor (etanercept) delayed the thrombus resolution in WT mice. Furthermore, TNF-\u03b1 treatment enhanced gene expression of\n              <jats:italic>Plau<\/jats:italic>\n              ,\n              <jats:italic>Mmp2<\/jats:italic>\n              , and\n              <jats:italic>Mmp9<\/jats:italic>\n              in WT macrophages but not\n              <jats:italic>Tnfrp5<\/jats:italic>\n              5\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              macrophages. These effects were significantly suppressed by ERK (extracellular signal regulated kinase) and NF-\u03baB (nuclear factor-kappa B) inhibitors. Therefore, the lack of TNF-Rp55 has detrimental roles in the thrombus resolution by suppressing PLAU, MMP-2, and MMP-9 expression. In contrast, TNF-\u03b1 administration accelerated thrombus resolution in WT but not\n              <jats:italic>Tnfrp5<\/jats:italic>\n              5\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>The TNF-\u03b1\u2013TNF-Rp55 axis may have essential roles in the resolution of venous thrombus in mice.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.118.311194","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T07:06:39Z","timestamp":1539327999000},"page":"2638-2650","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Contribution of the TNF-\u03b1 (Tumor Necrosis Factor-\u03b1)\u2013TNF-Rp55 (Tumor Necrosis Factor Receptor p55) Axis in the Resolution of Venous Thrombus"],"prefix":"10.1161","volume":"38","author":[{"given":"Mizuho","family":"Nosaka","sequence":"first","affiliation":[{"name":"From the Department of Forensic Medicine (M.N., Y.I., A.K., Y.K., T.K.), Wakayama Medical University, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Ishida","sequence":"additional","affiliation":[{"name":"From the Department of Forensic Medicine (M.N., Y.I., A.K., Y.K., T.K.), Wakayama Medical University, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Kimura","sequence":"additional","affiliation":[{"name":"From the Department of Forensic Medicine (M.N., Y.I., A.K., Y.K., T.K.), Wakayama Medical University, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Kuninaka","sequence":"additional","affiliation":[{"name":"From the Department of Forensic Medicine (M.N., Y.I., A.K., Y.K., T.K.), Wakayama Medical University, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Taruya","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (A.T.), Wakayama Medical University, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machi","family":"Furuta","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine (M.F.), Wakayama Medical University, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naofumi","family":"Mukaida","sequence":"additional","affiliation":[{"name":"Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Japan (N.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikazu","family":"Kondo","sequence":"additional","affiliation":[{"name":"From the Department of Forensic Medicine (M.N., Y.I., A.K., Y.K., T.K.), Wakayama Medical University, 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