Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells
Olof Gidlöf1, Marcel van der Brug, Jenny Ohman
1Department of Cardiology, Faculty of Medicine, Lund University, Lund, Sweden. olof.gidlof@med.lu.se
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.
Insights
Platelets in myocardial infarction (MI) patients lose specific microRNAs (miRNAs). Activated platelets release these miRNAs, which can regulate endothelial cell gene expression, impacting cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genomics
Background:
- Platelets are key in myocardial infarction (MI) pathogenesis, particularly at ruptured atherosclerotic plaques.
- MicroRNAs (miRNAs) are small non-coding RNAs with regulatory functions in gene expression.
- Understanding platelet miRNA profiles may reveal novel mechanisms in MI.
Purpose of the Study:
- To compare miRNA content in platelets from MI patients versus healthy controls.
- To investigate miRNA release from activated platelets.
- To determine if platelet-derived miRNAs regulate endothelial cell gene expression.
Main Methods:
- RNA sequencing (RNA-seq) to profile platelet miRNA.
- Platelet aggregation assays to study miRNA release.
- Fluorescently labeled miRNA and cell co-culture experiments to assess miRNA transfer to endothelial cells.
Main Results:
- Nine differentially expressed miRNAs were identified in MI patients' platelets, with eight showing decreased levels.
- Specific miRNAs (miR-22, -185, -320b, -423-5p) increased in platelet supernatant post-aggregation and were depleted in MI thrombi.
- Endothelial cells internalized miRNAs from activated platelets, and platelet miR-320b influenced endothelial intercellular adhesion molecule-1 expression.
Conclusions:
- Platelets from MI patients exhibit a distinct miRNA profile with significant depletion of certain miRNAs.
- Activated platelets release miRNAs that can be taken up by endothelial cells.
- Platelet-derived miRNAs may function as paracrine regulators of endothelial cell gene expression, contributing to MI pathogenesis.
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