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PRP was subjected to aggregometry using various agonists and processed to platelet releasates thereafter. Releasates, PPP, and platelets underwent real-time polymerase chain reactions to measure ncRNAs. Platelet ncRNA release appeared agonist-specific, dose-dependent, and inhibited by aspirin. Collagen triggered the strongest release for most ncRNAs, whereas miR-150 was hyperresponsive to ADP, and miR-21 was hyperresponsive to arachidonic acid. Comparing the dynamic range of ncRNA release to aggregation, aggregation reached a maximum at high agonist concentrations, while ncRNAs continued to rise. Cohort-wide associations showed that inflammation parameters like neutrophil counts and C-reactive protein correlated inversely with platelet aggregation and ncRNA release. Similarly, a high leucocyte-derived RNA content in isolated platelets correlated inversely with aggregation. Inverse correlations were absent in aspirin users. Through experiments on plasma-free platelet releasates and platelets, including size-exclusion chromatography, ultracentrifugation, and degradation assays, we discovered that microRNAs and YRNAs are carried by proteins and readily released, while circular-, long non-coding-, and messenger RNAs are carried by vesicles and preferentially retained. Finally, we assessed ncRNA responses to short- and long-term dual anti-platelet therapy (DAPT) in plasma from 265 patients with acute myocardial infarction (AMI) of the PACMAN-AMI trial. Most of the DAPT effect was already achieved by 4 weeks, with a further reduction at 52 weeks, revealing a short- and long-term DAPT effect not captured by aggregometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inflammation and leucocyte-derived RNAs in isolated platelets are associated with reduced platelet responses ex vivo, potentially reflecting exhaustion through pre-activation in vivo. We show that protein-bound ncRNAs are readily released from platelets, whereas vesicle-bound ncRNAs are preferentially retained. We highlight the potential of ncRNAs as biomarkers complementing aggregometry.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf100","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T07:31:45Z","timestamp":1748935905000},"page":"1392-1406","source":"Crossref","is-referenced-by-count":7,"title":["Platelets and inflammation\u2014insights from platelet non-coding RNA content and release in the Bruneck study and the PACMAN-AMI trial"],"prefix":"10.1093","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0675-8632","authenticated-orcid":false,"given":"Clemens","family":"Gutmann","sequence":"first","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna , Vienna ,","place":["Austria"]},{"name":"King\u2019s British Heart Foundation Centre, King\u2019s College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2279-8677","authenticated-orcid":false,"given":"Temo","family":"Barwari","sequence":"additional","affiliation":[{"name":"King\u2019s British Heart Foundation Centre, King\u2019s College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2643-7345","authenticated-orcid":false,"given":"Christian","family":"Schulte","sequence":"additional","affiliation":[{"name":"King\u2019s British Heart Foundation Centre, King\u2019s College London , London ,","place":["UK"]},{"name":"Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf , Hamburg ,","place":["Germany"]},{"name":"German Centre of Cardiovascular Research (DZHK), Partner Site Hamburg , Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6799-0553","authenticated-orcid":false,"given":"Konstantinos","family":"Theofilatos","sequence":"additional","affiliation":[{"name":"King\u2019s British Heart Foundation Centre, King\u2019s College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhawana","family":"Singh","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London , 86 Wood Ln, London W12 0BZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8642-6306","authenticated-orcid":false,"given":"Kaloyan","family":"Takov","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London , 86 Wood Ln, London W12 0BZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonca","family":"Suna","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart Center Z\u00fcrich , Z\u00fcrich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa V","family":"Chan","sequence":"additional","affiliation":[{"name":"The Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C","family":"Armstrong","sequence":"additional","affiliation":[{"name":"The Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Cassel","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London , 86 Wood Ln, London W12 0BZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Ueki","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Bern University Hospital, University of Bern , Bern ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas D","family":"H\u00e4ner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Bern University Hospital, University of Bern , Bern ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Santer","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Bruneck Hospital , Bruneck ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1866-7159","authenticated-orcid":false,"given":"Peter","family":"Willeit","sequence":"additional","affiliation":[{"name":"Institute of Clinical Epidemiology, Public Health, Health Economics, Medical Statistics and Informatics, Medical University of Innsbruck , Innsbruck ,","place":["Austria"]},{"name":"Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna , Vienna ,","place":["Austria"]},{"name":"Department of Public Health and Primary Care, University of Cambridge , Cambridge ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-2994","authenticated-orcid":false,"given":"Christian","family":"Hengstenberg","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0824-3026","authenticated-orcid":false,"given":"Lorenz","family":"R\u00e4ber","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Bern University 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