{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:40:19Z","timestamp":1786390819907,"version":"build-2736575974"},"reference-count":74,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010104","name":"Tianjin Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Current antiplatelet therapies effectively prevent thrombosis but are associated with an increased risk of bleeding, highlighting the need for safer alternatives. Ursodeoxycholic acid (UDCA) is a bile acid derivative with an established clinical safety profile, but its effects on platelet function and thrombosis remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>The effects of UDCA on platelet activation were assessed in human and mouse platelets in vitro and ex vivo. Antithrombotic efficacy and bleeding risk were evaluated in murine models of mesenteric arteriole injury and pulmonary embolism. Platelet activity was examined in healthy volunteers following oral administration, and clinical associations were explored in patients with acute coronary syndrome. Ligand\u2013receptor interactions were analysed using molecular docking and surface plasmon resonance, and mechanistic pathways were investigated using genetic and biochemical approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>UDCA inhibited platelet activation in both human and mouse platelets and reduced thrombus formation in vivo, with efficacy comparable to clopidogrel but significantly less bleeding. Oral administration suppressed platelet activation in healthy volunteers, and patients with acute coronary syndrome receiving UDCA exhibited lower serum troponin levels. UDCA directly bound to triggering receptor expressed on myeloid cells 2 (TREM2), and its antiplatelet effects were attenuated in TREM2\u2010deficient platelets. Mechanistically, UDCA enhanced Src homology 2 domain\u2010containing inositol phosphatase 1 (SHIP1) and suppressed Akt phosphorylation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These findings identify UDCA as a TREM2 agonist with antiplatelet and antithrombotic activity and a favourable bleeding profile, supporting its potential as a safer therapeutic strategy for thrombotic diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70567","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T02:07:11Z","timestamp":1782958031000},"page":"5566-5585","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ursodeoxycholic acid inhibits platelet activation and thrombosis via TREM2: Evidence from mouse models and human 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