{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:35:42Z","timestamp":1789094142461,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100003077","name":"Knowledge Foundation","doi-asserted-by":"publisher","award":["20190120"],"award-info":[{"award-number":["20190120"]}],"id":[{"id":"10.13039\/100003077","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003077","name":"Knowledge Foundation","doi-asserted-by":"publisher","award":["20220083"],"award-info":[{"award-number":["20220083"]}],"id":[{"id":"10.13039\/100003077","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":[[2025,3]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Pharmacological intervention of thrombosis is challenging, requiring a fined tune balance between beneficial antithrombotic effect versus risk of major bleeding complications. In this investigation, we elucidated the antithrombotic capacity of the novel 90\u2010mer RNA aptamer Apta\u20101 and its underlying mechanism of action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We utilized three independent <jats:italic>in vivo<\/jats:italic> animal models to establish antithrombotic activity and bleeding risk of Apta\u20101. Several cellular and molecular techniques were utilized to extensively characterize the effects of Apta\u20101 on primary and secondary haemostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Apta\u20101 significantly reduced thrombus weight in ferric chloride\u2010induced carotid artery thrombosis. A consistent reduction in thrombus weight was also observed in arteriovenous shunt thrombosis in rats, whereas tail bleeding time was unaffected. Cellular and molecular analyses revealed that Apta\u20101 interacted with thrombin, resulting in significant inhibition of protease\u2010activated receptor (PAR) signalling in platelets. On the other hand, Apta\u20101 shortened both thrombin generation and thrombin\u2010induced clotting times.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Apta\u20101 targets the heparin\u2010binding motif exosite II on thrombin leading to significant suppression of platelet PAR1 and PAR4 signalling. Intriguingly, Apta\u20101 produces substantial antithrombotic activity without anticoagulant or general antiplatelet properties. In fact, we found that Apta\u20101 accelerates the formation of blood clots and thus supports haemostasis without exhibiting typical anticoagulant properties. We suggest that Apta\u20101 may be a promising future drug candidate for treatment of thrombosis in diseases\/conditions where there are significant risks of serious bleeding complications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17382","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T23:30:12Z","timestamp":1733787012000},"page":"1358-1376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antithrombotic but not anticoagulant activity of the thrombin\u2010binding RNA aptamer Apta\u20101"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5000-3984","authenticated-orcid":false,"given":"Luiza","family":"Jedlina","sequence":"first","affiliation":[{"name":"Aptahem  Malm\u00f6 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