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Updated: Jun 28, 2025
Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
Ticagrelor downregulates the expression of proatherogenic and proinflammatory miR125-b compared to clopidogrel: A
Aleksandra Gasecka1, Ewelina Błażejowska1, Kinga Pluta2
11(st) Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
Insights
Ticagrelor treatment lowers miR-125b expression in acute myocardial infarction (AMI) patients compared to clopidogrel. This reduction in miR-125b may explain ticagrelor
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Pharmacology
Background:
- Ticagrelor, a P2Y12 antagonist, reduces cardiovascular mortality post-acute myocardial infarction (AMI) more than clopidogrel, but the mechanism remains unclear.
- Activated platelets release proatherogenic microRNAs (miRNAs), including miR-125a, miR-125b, and miR-223.
- This study hypothesized that ticagrelor therapy leads to lower expression of these specific miRNAs compared to clopidogrel.
Purpose of the Study:
- To compare the plasma expression levels of miR-125a, miR-125b, and miR-223.
- To investigate these miRNA levels in patients with AMI treated with either ticagrelor or clopidogrel.
Main Methods:
- Sixty patients with a first AMI, treated with aspirin and clopidogrel post-percutaneous coronary intervention, were randomized.
- Patients either switched to ticagrelor or continued clopidogrel treatment.
- Plasma miRNA expression (miR-223, miR-125a-5p, miR-125b) was quantified using qPCR at baseline, 72 hours, and 6 months. Platelet reactivity was assessed using multiple electrode aggregometry.
Main Results:
- miR-125b expression was significantly higher in AMI patients at 72 hours and 6 months compared to healthy volunteers (p=0.001).
- Ticagrelor treatment led to a decrease in miR-125b expression at 72 hours (p=0.007), returning to baseline by 6 months (p=0.005).
- miR-125a-5p and miR-223 expression levels were not significantly affected by switching from clopidogrel to ticagrelor.
Conclusions:
- Ticagrelor therapy results in reduced plasma miR-125b expression following AMI compared to clopidogrel.
- Elevated miR-125b levels may be associated with increased thrombotic events and poorer clinical outcomes observed in patients treated with clopidogrel.
- This finding suggests a potential mechanism for ticagrelor's superior clinical efficacy in AMI patients.
Background:
Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatory microRNAs, including miR-125a, miR-125b and miR-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel.
Objectives:
We compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel.
Methods:
After percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors.
Results:
Expression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor.
Conclusions:
Ticagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.
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