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Updated: Mar 18, 2026
Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
Expression of miRNA-26a in platelets is associated with clopidogrel resistance following coronary stenting
Shuxia Chen1, Xiaoyong Qi1, Hua Chen2
1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China; Department of Cardiology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
Insights
Platelet microRNA-26a expression is linked to clopidogrel resistance in patients undergoing coronary stenting. This finding may improve early diagnosis and prediction of resistance using combined miRNA and VASP PRI tests.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Genetics
Background:
- Clopidogrel resistance is a significant clinical issue in patients undergoing coronary stenting.
- Platelet microRNA (miRNA) expression is increasingly recognized for its role in drug response.
- Understanding the molecular mechanisms underlying clopidogrel resistance is crucial for optimizing antiplatelet therapy.
Purpose of the Study:
- To evaluate the association between platelet miRNA-26a expression and clopidogrel resistance.
- To investigate the role of VASP (vasodilator-stimulated phosphoprotein) in clopidogrel resistance.
- To explore the potential of miRNA and VASP PRI tests for early diagnosis of clopidogrel resistance.
Main Methods:
- Recruitment of 43 patients with coronary heart disease and 20 healthy volunteers.
- Measurement of VASP phosphorylation and platelet reactivity index (PRI) using flow cytometry.
- Assessment of VASP protein and mRNA expression via Western blotting and RT-qPCR.
- Determination of miRNA expression levels (miRNA-26a, miRNA-199, miRNA-23a) using RT-qPCR.
- Bioinformatic prediction of miRNA targets for VASP mRNA.
Main Results:
- Platelet activity was elevated in patients with low or high clopidogrel response compared to healthy subjects.
- VASP protein expression was elevated in patients with low clopidogrel response, while VASP mRNA levels were increased.
- Platelet miRNA-26a expression was significantly associated with high platelet reactivity and clopidogrel resistance.
- Serum miRNA levels did not show a significant association with clopidogrel resistance.
Conclusions:
- Platelet miRNA-26a plays a critical role in the development of clopidogrel resistance.
- Elevated VASP mRNA and protein expression are linked to low clopidogrel response.
- Combined testing of miRNA and VASP PRI may offer a valuable tool for early diagnosis and prediction of clopidogrel resistance.
Abstract:
The present study aimed to evaluate the association between platelet microRNA (miRNA)-26a expression and clopidogrel resistance in patients who underwent coronary stenting. Between September 2013 and August 2014, 43 patients with coronary heart disease underwent percutaneous coronary intervention at Heibei General Hospital (Shijiazhuang, China). In the same period, 20 healthy volunteers without any history of cardiovascular disease were enrolled in the present study as the control group. Flow cytometry was used to measure the phosphorylation levels of vasodilator-stimulated phosphoprotein (VASP), and to calculate the platelet reactivity index (PRI). Low response to clopidogrel was defined as PRI ≥50% on day 7 following clopidogrel administration. Western blotting was used to measure protein expression of VASP and reverse transcription-quantitative polymerase chain reaction analysis was performed to determine the expression levels of mRNA and miRNAs. Bioinformatics tools were employed to predict that miR-26a, miR-199 and miR-23a may target VASP mRNA. The results of the present study demonstrated that the activity of platelets in patients with low or high clopidogrel response was increased, as compared with healthy subjects. No differences in platelet VASP protein expression levels were detected between patients with high clopidogrel response and healthy subjects; whereas VASP protein expression was elevated in patients with low clopidogrel response. Furthermore VASP gene transcription was maintained at low levels in healthy subjects and patients with high clopidogrel response, whereas patients with low clopidogrel response exhibited increased VASP mRNA expression levels. Platelet expression of miRNA-26a, but not miRNA-199 or miRNA-23a, was associated with high platelet reactivity. Serum miRNA-26a, miRNA-199 and miRNA-23a were not demonstrated to be involved in clopidogrel resistance. Therefore, the present study demonstrated that platelet miRNA-26a has an important role in clopidogrel resistance. Combined miRNA and VASP PRI tests may aid the early diagnosis and prediction of clopidogrel resistance.
