A. Goldschmied1, B. Drotleff2, S. Winter3, E. Schaeffeler3, M. Schwab3, M. Gawaz1, T. Geisler1, D. Rath1
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1Innere Medizin III, Kardiologie und Kreislauferkrankungen, Universitätsklinikum Tübingen, Tübingen; 2Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Tübingen; 3Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tübingen, Stuttgart;
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Background: MicroRNAs (miRNA) are short endogenous RNAs that play important roles in post-transcriptional gene regulation. Little is known about platelet miRNAs in patients with coronary artery disease (CAD). The aim of the present study was to investigate platelet miRNAs in CAD and assess potential associations with functional myocardial recovery following myocardial infarction (MI).
Materials and
Methods: 62 platelet MiRNAs were measured in 100 CAD patients.
Expression profiles of patients with MI and chronic coronary syndrome (CCS)
were compared (MI n=33, CCS n=67). Furthermore, associations between miRNAs and
changes in systolic left ventricular ejection fraction (LVEF%) were analyzed.
In a second cohort of patients suffering from MI
(n=11), CCS (n=10) or no CAD (n=13), we measured miRNAs in platelets, platelet
supernatant and serum before and after in vitro platelet activation.
Results: Platelet miRNAs 103a-3p and 155-5p showed lower
expression in patients suffering from MI. Furthermore, miRNAs 103a-3p, 155-5p,
30a-5p, and 30b-5p, 30c-5p, 185-5p, 140-3p, 221-3p and 425-3p were
significantly lower expressed in MI patients compared to matched controls
(MCs). Additionally, 8 miRNAs showed lower expression levels in patients with
worsening of LVEF% in a 1-year follow-up period.
In the second cohort, we found significantly higher
concentrations of 30b-5p, 30c-5p, 103a-5p, 140-3p, 185-5p and 221-3p in the
platelet supernatant after activation across the three groups. Additionally,
miRNAs 30b-5p, 30c-5p, 103a-5p and 140-3p showed a higher abundance in serum of
MI as compared to CCS patients.
Conclusion: Distinct miRNAs show lower expression in platelets of
MI as compared to CCS patients. After in
vitro platelet activation, a release of miRNAs was observed. Interestingly,
upregulation of circulating miRNAs was found in MI patients when compared to
CCS patients and those without CAD. Hence, platelets may serve as a source of
upregulated circulating miRNAs and affect recovery of myocardial function after
MI.
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