{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T03:02:40Z","timestamp":1793415760541,"version":"4.5.0"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Foundation Walter Benjamine Programme","award":["537070747"],"award-info":[{"award-number":["537070747"]}]},{"name":"National Cancer Institute","award":["P30CA016087"],"award-info":[{"award-number":["P30CA016087"]}]},{"name":"NIH","award":["R35HL144993"],"award-info":[{"award-number":["R35HL144993"]}]},{"name":"NIH","award":["R01 HL139909"],"award-info":[{"award-number":["R01 HL139909"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["16SFRN2873002"],"award-info":[{"award-number":["16SFRN2873002"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,22]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Platelets are increasingly recognized as active participants in immune signaling and systemic inflammation. Upon activation, platelets form monocyte platelet aggregates (MPA) representing the crossroads of thrombosis and inflammation. We hypothesized that platelet transcriptomics could capture this thromboinflammatory axis and identify individuals at elevated cardiovascular risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS: MPA levels, defined as CD14+CD61+ cells, were measured using flow cytometry at 2 time points, 4 weeks apart, in healthy individuals<\/jats:title>\n                    <jats:p>\n                      Platelets were isolated and sequenced. Individuals were categorized as MPA\n                      <jats:sup>hi<\/jats:sup>\n                      or MPA\n                      <jats:sup>lo<\/jats:sup>\n                      based on consistently high or low MPA levels across time points.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Among 149 participants (median age 52 years, 57% female, 50% non-White), MPA\n                      <jats:sup>hi<\/jats:sup>\n                      individuals exhibited increased expression of platelet activation markers P-selectin (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001), PAC-1 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.021), and CD40L (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001) and enriched immune signaling pathways. Informed by MPA levels and derived from the platelet transcriptome, we developed a 42-gene thromboinflammation platelet signature (TIPS), which correlated with MPA levels in multiple cohorts and was reproducible over time. TIPS was elevated in patients with COVID-19 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.0002) and myocardial infarction (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>adj<\/jats:sub>\n                      = 0.008), and as in predicted future cardiovascular events in patients who underwent lower extremity revascularization after a median follow-up of 18 months (adjusted for age, sex, race, and ethnicity [adjHR] 1.55,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.006). Notably, TIPS was modifiable by ticagrelor (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.002) but not aspirin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>These findings establish MPA as a biomarker of thromboinflammation and introduce TIPS, a platelet RNA signature, that captures thromboinflammation and provides a promising tool for cardiovascular risk stratification and a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>NCT04369664<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>NIH R35HL144993, NIH R01HL139909, and AHA 16SFRN2873002 to JSB, DFG Walter-Benjamin-Programme 537070747 to AB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.195824","type":"journal-article","created":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T19:00:44Z","timestamp":1766343644000},"source":"Crossref","is-referenced-by-count":9,"title":["A platelet transcriptomic signature of thromboinflammation predicts cardiovascular risk"],"prefix":"10.1172","volume":"10","author":[{"given":"Antonia","family":"Beitzen-Heineke","sequence":"first","affiliation":[{"name":"Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA."},{"name":"Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Muller","sequence":"additional","affiliation":[{"name":"Precision Medicine in the Department of Medicine,"},{"name":"Institute for Systems Genetics, NYU Grossman School of 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