MiR-223 or miR-126 predicts resistance to dual antiplatelet therapy in patients with ST-elevation myocardial infarction

Figures

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  Figure 1.. Patient selection in this study. A total of 120 consecutive patients with STEMI were included in the present study. Responses to clopidogrel were determined by the VerifyNow method. Thirty-six patients had a PRU larger than 208 U and were considered resistant to DAPT (referred to as non-responders), and the remaining patients were responders. STEMI, ST-elevation myocardial infarction; PRU, P2Y12 reaction units; DAPT, dual antiplatelet therapy.

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  Figure 2.. Association of plasma miR-223/miR-126 levels with resistance to DAPT. a. Serum levels of miR-223 in responders and non-responders before DAPT. b. Serum levels of miR-126 in responders and non-responders before DAPT. c. Correlation between PRU and relative miR-223 levels in the serum. d. Correlation between PRU and relative miR-126 levels in the serum. ****p < 0.0001, by two-tailed Student t-tests. STEMI, ST-elevation myocardial infarction; PRU, P2Y12 reaction units; DAPT, dual antiplatelet therapy.

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  Figure 3.. Patients with low levels of miR-223 or miR-126 have shorter cardiac-event-free survival. All recruited patients were followed up since the initial administration for up to 24 months. A composite endpoint of heart disease-related death, recurrent ACS, and heart failure was evaluated. a. Patients with low miR-223 levels in the serum had shorter cardiac-event-free survival. b. Patients with low miR-126 levels in the serum had shorter cardiac-event-free survival. ACS, acute coronary syndrome.

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  Figure 4.. Modulating miR-223 or miR-126 in vitro changed the PRU. a. miR-223 oe plasmid transfection of platelets collected from patients in the decreased miR-223 group reduced the PRU. b. miR-223 siRNA transfection of platelets collected from those in the elevated miR-223 group increased the PRU. c. miR-126 oe plasmid transfection of platelets collected from those in the decreased miR-126 group reduced the PRU. d. miR-126 miRNA transfection of platelets collected from those in the elevated miR-126 group increased the PRU. **p < 0.01; ****p < 0.0001, by two-tailed Student t-tests. Each dot represents the mean of triplicate samples for each individual. PRU, P2Y12 reaction units; CTR, control; oe, overexpression; kd, knockdown.

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  Figure 5.. Modulating miR-223 or miR-126 in vitro regulated platelet aggregation in the presence of clopidogrel. a. Transfecting miR-223 plasmids into platelets collected from those in the decreased miR-223 group reduced platelet aggregation in the presence of clopidogrel. b. Knockdown of miR-223 in platelets collected from those in the elevated miR-223 group increased platelet aggregation in the presence of clopidogrel. c. Transfecting miR-126 plasmids into platelets collected from those in the decreased miR-126 group reduced platelet aggregation in the presence of clopidogrel. d. Knockdown of miR-126 in platelets collected from those in the elevated miR-126 group increased platelet aggregation in the presence of clopidogrel. ****p < 0.001, by one-way ANOVA with Bonferroni post-hoc tests. ADP, adenosine 5ʹ-diphosphate; CTR, control; oe, overexpression; kd, knockdown.