Key result
Low platelet miR-144-5p is linked to poor aspirin response and higher serum thromboxane B2.
Why the study?
Interindividual variability in low-dose aspirin response contributes to residual platelet activation and thrombotic risk, but mechanistic insights into how platelet microRNAs modulate aspirin pharmacodynamics remain limited.
Does platelet miR-144-5p regulate COX-1/2 expression and modulate aspirin response in patients with cardiometabolic risk?
Observational (n=200)
Does platelet miR-144-5p regulate COX-1/2 expression and modulate aspirin response in patients with cardiometabolic risk?
Effect estimate: ρ=-0.235
p-value: p=0.007
Low platelet miR-144-5p is associated with accelerated COX-1 recovery and poor aspirin response, providing a mechanistic explanation for interindividual variability in antiplatelet efficacy.
May inform biomarker development for aspirin response variability; hypothesis-generating for miR-144-5p regulation of COX-1 in cardiometabolic patients.
Interindividual variability in response to low-dose aspirin (ASA) contributes to residual platelet activation and thrombotic risk. Platelet microRNAs (miRNAs) may modulate ASA pharmacodynamics, but mechanistic insights remain limited. To investigate whether platelet miR-144-5p regulates cyclooxygenase 1/2 (COX-1/2) expression and modulates ASA response in cardiometabolic patients. Two hundred ASA-treated patients were stratified into tertiles of serum thromboxane B 2 (sTXB 2 ) slope, an ex vivo marker of COX-1 recovery. Platelet and extracellular vesicle miR-144-5p levels were quantified by RT-qPCR and correlated with biochemical and clinical variables. Functional studies were performed in megakaryocytic (DAMI) and endothelial (HUVEC) cells transfected with miR-144-5p mimics or inhibitors to assess COX-1/2 regulation. Patients with poor ASA response (3rd tertile of sTXB 2 slope) exhibited reduced platelet miR-144-5p (p=0.027) and higher COX-1 mRNA/protein levels (p≤0.027), whereas miR-144-5p was enriched in platelet-derived extracellular vesicles. Platelet miR-144-5p was inversely correlated with sTXB 2 (ρ=-0.235, p=0.007) and COX-1/2 mRNA expression. In DAMI (human megakaryocyte) cells, ASA exposure upregulated miR-144-5p cells; in addition, miR-144-5p overexpression suppressed, and inhibition enhanced, COX-1 protein levels. Similar effects were observed in HUVECs, where miR-144-5p downregulated both COX-1 and COX-2. Among our patients, platelet miR-144-5p were lower in those with obesity, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease, conditions known to affect aspirin response. Platelet miR-144-5p directly regulates COX-1/2 expression in vitro and is associated with interindividual variability in ASA response. Low platelet miR-144-5p identifies patients with accelerated COX-1 recovery and residual thromboxane generation, providing a potential mechanistic framework for precision antiplatelet therapy and potential miRNA-targeted interventions.
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Simeone et al. (2026) conducted an observational in Cardiometabolic risk (n=200). Low platelet miR-144-5p vs. High platelet miR-144-5p was evaluated on Serum thromboxane B2 (sTXB2) levels (ρ=-0.235, p=0.007). Low platelet miR-144-5p is associated with poor aspirin response and inversely correlates with serum thromboxane B2 levels (ρ=-0.235, p=0.007) in patients with cardiometabolic risk.
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