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Circulating miR-223-3p as an Independent Biomarker of Recurrent Thrombotic Risk After Ischemic Stroke
Bence Balczó1, Katalin Maricza2, Krisztina Molnár2
1Department of Pediatric Care, Csolnoky Ferenc Hospital, 8200 Veszprém, Hungary.
Abstract:
Background: Circulating microRNAs (miRNAs) have emerged as potential biomarkers of platelet reactivity and thrombotic risk. Among them, miR-223-3p regulates P2Y12 receptor expression and may influence response to antiplatelet therapy. This study aimed to evaluate the prognostic value of selected circulating miRNAs in post-stroke patients receiving antiplatelet treatment. Methods: Sixty ischemic stroke survivors were prospectively enrolled and followed for 18 months for recurrent vascular events (stroke, transient ischemic attack, or myocardial infarction). Plasma levels of miR-126-3p, miR-223-3p, miR-24-3p, and miR-199a-5p were quantified using reverse transcription real-time PCR. Clinical data, antiplatelet regimen, statin use, and Essen Stroke Risk Scores (ESRS) were recorded. Logistic regression was applied to identify independent predictors of thrombotic events. Results: Expression of all examined miRNAs differed significantly across treatment groups. The dual antiplatelet therapy (DAPT) group showed the highest levels of miR-126-3p and miR-199a-5p (p < 0.01). Within the statin-naïve DAPT subgroup, lower miR-199a-5p levels (p < 0.001) were observed among patients who experienced ischemic events (n = 7/60; 12%; stroke = 4, TIA = 2, ACS = 1) during 18 months of follow-up. In multivariate analysis, reduced miR-223-3p remained the only independent predictor of recurrent thrombotic events (OR 1.18, 95% CI 1.01-1.37, p = 0.036), independent of ESRS and platelet reactivity. Elevated miR-126-3p and miR-199a-5p were associated with favorable treatment response, particularly among statin users. Conclusions: This study identifies low circulating miR-223-3p as an independent biomarker of thrombotic risk in post-stroke patients, potentially reflecting enhanced platelet activation via P2Y12 signaling. In contrast, higher miR-126-3p and miR-199a-5p levels may indicate more effective antiplatelet response. These findings support the potential utility of miRNA profiling for individualized antiplatelet therapy and long-term risk stratification after ischemic stroke.
Insights
Low levels of microRNA-223-3p (miR-223-3p) predict a higher risk of recurrent thrombotic events in stroke patients. Higher miR-126-3p and miR-199a-5p suggest a better response to antiplatelet therapy.
Area of Science:
- Biochemistry
- Genetics
- Cardiovascular Medicine
Background:
- Circulating microRNAs (miRNAs) are emerging biomarkers for platelet reactivity and thrombotic risk.
- miR-223-3p is implicated in regulating P2Y12 receptor expression and antiplatelet therapy response.
Purpose of the Study:
- To assess the prognostic value of selected circulating miRNAs in post-stroke patients undergoing antiplatelet treatment.
- To identify miRNA biomarkers for predicting recurrent vascular events.
Main Methods:
- Prospective enrollment of 60 ischemic stroke survivors followed for 18 months.
- Quantification of plasma miR-126-3p, miR-223-3p, miR-24-3p, and miR-199a-5p via RT-qPCR.
- Analysis of clinical data, antiplatelet regimens, statin use, and Essen Stroke Risk Scores (ESRS).
Main Results:
- miR-223-3p was identified as the sole independent predictor of recurrent thrombotic events (OR 1.18, 95% CI 1.01-1.37, p=0.036).
- Lower miR-199a-5p levels correlated with ischemic events in statin-naïve dual antiplatelet therapy (DAPT) patients.
- Elevated miR-126-3p and miR-199a-5p were linked to favorable treatment response, especially in statin users.
Conclusions:
- Low circulating miR-223-3p is an independent biomarker for thrombotic risk in post-stroke patients, possibly indicating increased platelet activation.
- Higher miR-126-3p and miR-199a-5p levels may signify enhanced antiplatelet response.
- miRNA profiling holds potential for personalized antiplatelet therapy and risk stratification in stroke survivors.
