TY - JOUR
T1 - Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression
AU - Gidlöf, Olof
AU - Van Der Brug, Marcel
AU - Öhman, Jenny
AU - Gilje, Patrik
AU - Olde, Björn
AU - Wahlestedt, Claes
AU - Erlinge, David
N1 - Funding Information:
This work was supported by the Swedish Heart and Lung Foundation, Swedish Scientific Research Council (521-2009-2276), governmental funding of clinical research within the Swedish National Health Service, and Lund University Hospital funds.
Funding Information:
The authors thank Karin Wallmark and Hel?n Brogren of the Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, University of Gothenburg for preparation of platelet releasate, and Siv Svensson of the Department of Cardiology, Lund University, for assistance with blood sampling and preparation of platelets. This work was supported by the Swedish Heart and Lung Foundation, Swedish Scientific Research Council (521-2009-2276), governmental funding of clinical research within the Swedish National Health Service, and Lund University Hospital funds.
PY - 2013/5/9
Y1 - 2013/5/9
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2012-10-461798
DO - 10.1182/blood-2012-10-461798
M3 - Article
C2 - 23493781
AN - SCOPUS:84880466686
VL - 121
SP - 3908
EP - 3917
JO - Blood
JF - Blood
SN - 0006-4971
IS - 19
ER -