CO077 | PLATELET MIR-144-5P REGULATES COX-1/2 EXPRESSION AND MODULATES ASPIRIN RESPONSE IN PATIENTS WITH CARDIOMETABOLIC RISK
Abstract
Background and Aims. 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 (COX)-1/2 expression and modulates ASA response in cardiometabolic patients. Methods. Two hundred ASA-treated patients were stratified into tertiles of serum thromboxane B₂ (sTXB₂) 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. Results. Patients with poor ASA response (3rd tertile of sTXB₂ 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 sTXB₂ (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 was lower in those with obesity, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease, conditions known to affect aspirin response. Conclusions. Platelet miR-144-5p directly regulates COX-1/2 expression and contributes to interindividual variability in ASA response. Low platelet miR-144-5p identifies patients with accelerated COX-1 recovery and residual thromboxane generation, providing a mechanistic basis for precision antiplatelet therapy and potential miRNA-targeted interventions.
Related
- Cannabigerol Modulates Blood Pressure and Vascular Reactivity in a Rat Model of Hypertension and Platelet Responses in Human Blood In Vitro
- Increasing plant protein sources in the diet modulates gut microbiota and tryptophan metabolism in men at cardiometabolic risk
- 1161 Novel IL1RAP expression gradient modulates the myeloid cell phenotype and T-cell infiltration patterns of the Ewing sarcoma immune microenvironment
- An enhancer-like region regulates hrp3 promoter stage-specific gene expression in the human malaria parasite Plasmodium falciparum
- THE MULTIFUNCTIONAL PROTEIN E4F1 REGULATES MELANOCYTIC FUNCTIONS IN MICE THROUGH PROTEIN TRANSLATION AND MITF EXPRESSION
BibTeX
@article{simeone2026co077,
title = {{CO077 | PLATELET MIR-144-5P REGULATES COX-1/2 EXPRESSION AND MODULATES ASPIRIN RESPONSE IN PATIENTS WITH CARDIOMETABOLIC RISK}},
author = {Paola Giustina Maria Simeone},
journal = {Bleeding, Thrombosis and Vascular Biology},
year = {2026},
month = oct,
url = {https://www.btvb.org/btvb/article/view/779},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - CO077 | PLATELET MIR-144-5P REGULATES COX-1/2 EXPRESSION AND MODULATES ASPIRIN RESPONSE IN PATIENTS WITH CARDIOMETABOLIC RISK
AU - Paola Giustina Maria Simeone
PY - 2026
DA - 2026/10/26
JO - Bleeding, Thrombosis and Vascular Biology
UR - https://www.btvb.org/btvb/article/view/779
AB - Background and Aims. 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 (COX)-1/2 expression and modulates ASA response in cardiometabolic patients. Methods. Two hundred ASA-treated patients were stratified into tertiles of serum thromboxane B₂ (sTXB₂) 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. Results. Patients with poor ASA response (3rd tertile of sTXB₂ 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 sTXB₂ (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 was lower in those with obesity, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease, conditions known to affect aspirin response. Conclusions. Platelet miR-144-5p directly regulates COX-1/2 expression and contributes to interindividual variability in ASA response. Low platelet miR-144-5p identifies patients with accelerated COX-1 recovery and residual thromboxane generation, providing a mechanistic basis for precision antiplatelet therapy and potential miRNA-targeted interventions.
SN - 2785-5309
ER -