{
  "abstract": "AIM: The fibrinolytic system may protect against or promote atherosclerosis; however, the effects of distinct antifibrinolytic interventions on plaque development and extracellular matrix (ECM) remodeling remain unclear. METHODS: We compared YO-2, a direct plasmin inhibitor, and tranexamic acid (TXA), a lysine analog that interferes with plasminogen/plasmin binding to fibrin, in Apoe/Ldlr double-knockout mice fed a Western diet. The atherosclerotic burden, plaque structure, vascular marker expression, leukocyte-endothelial interactions, and nitric oxide (NO)-related indices were assessed. RESULTS: YO-2 significantly increased the atherosclerotic lesion area compared to the control, whereas TXA had minimal effects. The thrombolytic activity in the He-Ne laser-induced thrombosis model and NO-related indices did not differ significantly among the groups. Vascular t-PA expression increased in both treatment groups. YO-2 was associated with reduced uPAR and MMP-9 expression and preservation of the internal elastic lamina and medial elastin fibers, suggesting reduced pericellular ECM degradation. TXA increased PAI-1 and TAFI expression without altering uPAR. Both treatments significantly reduced leukocyte rolling, and the E-selectin expression was significantly decreased with YO-2, with a similar trend with TXA. eNOS mRNA expression was significantly higher in both groups, although the corresponding increase in the eNOS protein expression was only a non-significant trend. CONCLUSIONS: Direct plasmin inhibition with YO-2 aggravated atherosclerosis and it was associated with a reduced uPAR/MMP-9 expression and altered vascular ECM remodeling. TXA had limited effects on lesion burden while increasing PAI-1 and TAFI expression. These findings suggest that direct plasmin inhibition and TXA-mediated antifibrinolysis may differentially affect atherosclerosis and vascular remodeling.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Natsumi Yoshihama"
    },
    {
      "name": "Nana Kurisu"
    },
    {
      "name": "Kentaro Shimatani"
    },
    {
      "name": "Kanae Hyodo"
    },
    {
      "name": "Naotaka Ohta"
    },
    {
      "name": "Hiromitsu Ishii"
    },
    {
      "name": "Tsutomu Yamashita"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aab6zdtqv7wpk.bib",
  "cited_by": 0,
  "doi": "10.5551/jat.66328",
  "fulltext_url": "https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66328/_article",
  "id": "aab6zdtqv7wpk",
  "issns": [
    "1880-3873",
    "1340-3478"
  ],
  "landing_url": "https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66328/_article",
  "language": null,
  "licence": "CC-BY-NC-SA",
  "licence_label": "CC BY-NC-SA",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-sa/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "jstage-journal",
      "medicine/cardiovascular"
    ],
    [
      "openalex",
      "2403|Atherosclerosis and Cardiovascular Diseases"
    ]
  ],
  "openalex": "W7221782263",
  "pdf_url": "https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66328/_pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/aab6zdtqv7wpk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.5551/jat.66328",
      "source": "jstage",
      "url": "https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66328/_article"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Atherosclerosis and Cardiovascular Diseases",
      "subfield": "immunology"
    }
  ],
  "title": "Differential Effects of Direct Plasmin Inhibition and Tranexamic Acid on Atherosclerosis Progression and Vascular Remodeling in Apoe/Ldlr Double-Knockout Mice",
  "title_text": "Differential Effects of Direct Plasmin Inhibition and Tranexamic Acid on Atherosclerosis Progression and Vascular Remodeling in Apoe/Ldlr Double-Knockout Mice",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/aab6zdtqv7wpk",
  "venue": "Journal of Atherosclerosis and Thrombosis",
  "versions": []
}