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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Res+Pract+Thromb+Haemost 2018 ; 2 (3): 596-606 Nephropedia Template TP
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MiR?21 role in aspirin?dependent PPAR? and multidrug resistance protein 4 upregulation #MMPMID30046765
Massimi I; Alemanno L; Guarino ML; Guerriero R; Frati L; Biasucci L; Pulcinelli FM
Res Pract Thromb Haemost 2018[Jul]; 2 (3): 596-606 PMID30046765show ga
Background: A 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 PPAR??dependent mechanism and reduces miR?21 expression that, in turn, downregulates PPAR? expression. Objective: The aim of our study was to verify the relationship between miR?21 and MRP4?PPAR? levels induced by aspirin treatment. Methods: We evaluated the changes in MRP4?PPAR?, 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). Results: We observed an aspirin?induced reverse relationship between the expression of miR?21 and PPAR??MRP4. In DAMI cells the miR?21 mimic transfection reduces PPAR? and MRP4 expression, even if cells were treated with aspirin after transfection. MiR?21 inhibitor transfection induces PPAR? 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. Conclusion: The 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.