ArticleResearch and practice in thrombosis and haemostasis2018
MiR-21 role in aspirin-dependent PPARα and multidrug resistance protein 4 upregulation.
Article in Research and practice in thrombosis and haemostasis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 10 citations in OpenAlex.
- Circulating S100A8/A9 drives faster platelet COX-1 recovery via MRP4, impairing the duration of aspirin response.Blood advances · 2026Article
- Noncoding RNA Roles in Pharmacogenomic Responses to Aspirin: New Molecular Mechanisms for an Old Drug.BioMed research international · 2021Review
- Platelet activation and multidrug resistance protein-4 expression in children and adolescents with different subtypes of primary thrombocythemia.Haematologica · 2020Article
- MiR-21 role in aspirin-dependent PPARα and multidrug resistance protein 4 upregulation.Research and practice in thrombosis and haemostasis · 2018Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA mechanism involved in high on-aspirin treatment residual platelet reactivity is platelet multidrug resistance protein 4 (MRP4) overexpression. Aspirin enhances platelet MRP4 expression with a PPARα-dependent mechanism and reduces miR-21 expression that, in turn, downregulates PPARα expression.
objectiveThe aim of our study was to verify the relationship between miR-21 and MRP4-PPARα levels induced by aspirin treatment.
methodsWe evaluated the changes in MRP4-PPARα, mRNA, MRP4 protein, and miR-21 expression induced by aspirin in: (i) in vitro-treated megakaryoblastic cell line (DAMI), (ii) primary megakaryocytes cultures and derived platelets, (iii) healthy volunteers' platelets treated with aspirin, and (iv) aspirinated patients (aspirin-treated patients) and in a control population (control).
resultsWe observed an aspirin-induced reverse relationship between the expression of miR-21 and PPARα-MRP4. In DAMI cells the miR-21 mimic transfection reduces PPARα and MRP4 expression, even if cells were treated with aspirin after transfection. MiR-21 inhibitor transfection induces PPARα and MRP4 expression that are not enhanced by aspirin treatment. In human megakaryocytes, aspirin treatment lead to a miR-21 downregulation and a MRP4 upregulation and this trend is confirmed in derived platelets. In aspirin-treated volunteers, an inverse relationship between miR-21 and MRP4 platelet expression was found after aspirin treatment. A similar negative relationship was found in aspirin-treated patients vs the control population.
conclusionThe results reported in this study provide information that aspirin induces the modulation of platelet miR-21 expression levels and this modulation can be responsible for MRP4 enhancement in circulating platelets.
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