biostudies-literatureUnknown10(4)Liani R<h4>Abstract</h4>Low-dose aspirin is a cornerstone of cardiovascular prevention in high-risk patients, inhibiting platelet cyclooxygenase (COX-1) and reducing thromboxane A2 (TXA2) production for 24 hours. However, the duration of this effect varies among individuals, and the role of inflammation and platelet microRNAs in this variability remains unclear. This study identifies a thromboinflammatory mechanism linked to shorter duration of TXB2 suppression during aspirin therapy. This mechanism involves (1) elevated circulating S100A8/A9, indicating systemic inflammation; (2) reduced platelet microRNA-21-5p (miR-21-5p) and increased circulating miR-21-5p (c-miR-21-5p), suggesting altered microRNA regulation; (3) S100A8/A9-driven upregulation of platelet multidrug resistance protein 4 (MRP4);Blood advances1236-1249https://www.ebi.ac.uk/biostudies/studies/S-EPMC12925102biostudies-literatureCirculating S100A8/A9 drives faster platelet COX-1 recovery via MRP4, impairing the duration of aspirin response.PMC12925102Liani RSimeone PGFrezza MLuongo MPulcinelli FSantilli FLattanzio SCiotti SRicci ACipollone FAlfonsetti MfalseCirculating S100A8/A9 drives faster platelet COX-1 recovery via MRP4, impairing the duration of aspirin response.<h4>Abstract</h4>Low-dose aspirin is a cornerstone of cardiovascular prevention in high-risk patients, inhibiting platelet cyclooxygenase (COX-1) and reducing thromboxane A2 (TXA2) production for 24 hours. However, the duration of this effect varies among individuals, and the role of inflammation and platelet microRNAs in this variability remains unclear. This study identifies a thromboinflammatory mechanism linked to shorter duration of TXB2 suppression during aspirin therapy. This mechanism involves (1) elevated circulating S100A8/A9, indicating systemic inflammation; (2) reduced platelet microRNA-21-5p (miR-21-5p) and increased circulating miR-21-5p (c-miR-21-5p), suggesting altered microRNA regulation; (3) S100A8/A9-driven upregulation of platelet multidrug resistance protein 4 (MRP4);2026-01-01T00:00:00Z2026 Feb2026-07-16T15:17:01.659Z2026-07-11T03:06:49.516ZS-EPMC129251024129598410.1182/bloodadvances.2025017653