{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:00:56Z","timestamp":1780408856542,"version":"3.54.1"},"reference-count":25,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging is associated with enhanced platelet activation that may contribute to the occurrence of cardiovascular events. However, the mechanism linking aging with platelet activation is not fully understood. The objective of this study is to investigate the relationship between aging, platelet Cox-1 expression, and thromboxane (Tx) B2 production in patients with atrial fibrillation. Serum Cox-1 and TxB2 were measured in 134 patients with atrial fibrillation. Correlations were assessed between age, Cox-1, and TxB2. A robust mediation analysis evaluated whether Cox-1 mediates the association between age and TxB2. In vitro experiments were performed in 20 patients to evaluate the effect of aspirin on platelet TxB2 production and to quantify platelet Cox-1 expression across age groups (i.e., &lt; or \u226565 years). Serum Cox-1 and TxB2 progressively increased by decades of age. A positive and significant correlation was found between age and Cox-1 (R = 0.42, p-values &lt; 0.01), age and TxB2 values (R = 0.44, p-value &lt; 0.01), and Cox-1 and TxB2 (R = 0.5, p-value &lt; 0.01). Cox-1 partially and significantly mediated the effect of age on TxB2 (\u03b2 = 5.23, 95% confidence interval [2.33\u20138.63]) for the effect of age on TxB2. In vitro analysis showed a reduced inhibitory effect of aspirin on platelet TxB2 production in old compared to young subjects (IC50 97 \u03bcM and 49 \u03bcM in \u2265 and &lt;65 years, respectively) that was paralleled by Cox-1 overexpression in patients \u226565 years. Platelet Cox-1 expression was inversely related with aspirin inhibitory effects (R = \u22120.640, p-value &lt; 0.01). Aging is associated with a concomitant increase in Cox-1 concentration and TxB2 production and an impaired ability of aspirin to inhibit Cox-1.<\/jats:p>","DOI":"10.3390\/ijms27114972","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-Related Platelet Cox-1 Upregulation in Atrial Fibrillation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-3214","authenticated-orcid":false,"given":"Emanuele","family":"Valeriani","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Endocrine and Metabolic Sciences, and Infectious Diseases, Azienda Ospedaliero-Universitaria Policlinico Umberto I, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1966-5945","authenticated-orcid":false,"given":"Vittoria","family":"Cammisotto","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9467-5903","authenticated-orcid":false,"given":"Danilo","family":"Menichelli","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical Specialty, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-5213","authenticated-orcid":false,"given":"Daniele","family":"Pastori","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"},{"name":"Scientific Institute for Research, Hospitalization and Healthcare IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6455-4828","authenticated-orcid":false,"given":"Valentina","family":"Castellani","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-3059","authenticated-orcid":false,"given":"Simona","family":"Bartimoccia","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Cucchiara","sequence":"additional","affiliation":[{"name":"Internal Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-7626","authenticated-orcid":false,"given":"Arianna","family":"Pannunzio","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical Specialty, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5749-786X","authenticated-orcid":false,"given":"Ilaria Maria","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical Specialty, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ombretta","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Surgery \u201cParide Stefanini\u201d-Policlinico Umberto I, Vascular Surgery Division, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6216-9595","authenticated-orcid":false,"given":"Roberto","family":"Carnevale","sequence":"additional","affiliation":[{"name":"Scientific Institute for Research, Hospitalization and Healthcare IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Violi","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2265-7455","authenticated-orcid":false,"given":"Pasquale","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ciumarnean, L., Milaciu, M.V., Negrean, V., Orasan, O.H., Vesa, S.C., Salagean, O., Ilut, S., and Vlaicu, S.I. 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