title: Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression.
abstract: Platelets play a crucial role in the pathogenesis of myocardial infarction (MI) by adhering to the site of a ruptured atherosclerotic plaque. The aim of this study was to screen for differences in the micro RNA (miRNA) content of platelets from patients with myocardial infarction and control patients, to investigate a possible release of miRNAs from activated platelets and to elucidate whether platelet-derived miRNAs could act as paracrine regulators of endothelial cell gene expression. Using RNA-seq, we found 9 differentially expressed miRNAs in patients compared with healthy controls, of which 8 were decreased in patients. Of these, miR-22, -185, -320b, and -423-5p increased in the supernatant of platelets after aggregation and were depleted in thrombi aspirated from MI patients, indicating the release of certain miRNAs from activated platelets. To confirm that endothelial cells could take up the released platelet miRNAs, transfer of both fluorescently labeled miRNA and exogenous cel-miR-39 from activated platelets to endothelial cells was shown. Finally, a possible paracrine role of released platelet miR-320b on endothelial cell intercellular adhesion molecule-1 expression was shown. Thus, platelets from patients with MI exhibit loss of specific miRNAs, and activated platelets shed miRNAs that can regulate endothelial cell gene expression.
authors.affiliation: Department of Cardiology, Faculty of Medicine, Lund University, Lund, Sweden. olof.gidlof@med.lu.se
authors.forename: Olof
authors.initials: O
authors.lastname: Gidlöf
authors.forename: Marcel
authors.initials: M
authors.lastname: van der Brug
authors.forename: Jenny
authors.initials: J
authors.lastname: Ohman
authors.forename: Patrik
authors.initials: P
authors.lastname: Gilje
authors.forename: Björn
authors.initials: B
authors.lastname: Olde
authors.forename: Claes
authors.initials: C
authors.lastname: Wahlestedt
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
mesh_terms: D001792:Blood Platelets / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D015539:Platelet Activation / Q000235:genetics* / Q000502:physiology; D010974:Platelet Aggregation / Q000235:genetics; D059467:Transcriptome
chemical_list: C573420:ICAM1 protein, human; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; D018799:Intercellular Adhesion Molecule-1