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Thromb Res. 2013 Jun;131(6):508-13. doi: 10.1016/j.thromres.2013.02.015. Epub 2013 Mar 15.

Decreased platelet miR-223 expression is associated with high on-clopidogrel platelet reactivity.

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1
Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, China.

Abstract

OBJECTIVES:

We aimed to investigate the relationship between platelet microRNA (miR-223 and miR-96) expression and clopidogrel responsiveness in patients with coronary heart disease (CHD).

MATERIALS AND METHODS:

A total of 33 consecutive non-diabetic CHD patients scheduled for percutaneous coronary intervention were enrolled. Platelet reactivity after clopidogrel loading dose (300 mg) was determined by two methods [platelet reactivity index (PRI), measured by vasodilator-stimulated phosphoprotein (VASP) phosphorylation flow cytometry and ADP-induced platelet aggregation (PAG), measured by light transmission aggregometry]. Total platelet RNA was isolated from purified platelets (CD45 magnetic bead negative selection) to quantify miR-223 and miR-96 expression by real-time PCR.

RESULTS:

All subjects were dichotomized according to PRI medians (normal-responders: PRI < 56.5%, n = 17 and low-responders: PRI > 56.5%, n = 16) and PAG medians (normal-responders: PAG < 43%, n = 17 and low-responders: PAG > 43%, n = 16). Compared with PRI-determined normal-responders, miR-223 expression, but not miR-96, was significantly decreased in low-responders (P = 0.037). No differential expression of miR-223 and miR-96 was observed via PAG determination between normal- and low-responders. In addition, miR-223 expression, but not miR96, was statistically correlated with PRI (Spearman r = -0.403, P = 0.020). Stepwise binary logistic regression analysis revealed that among factors that potentially influence platelet reactivity (CYP2C19*2 loss-of-function genotypes, use of calcium channel blockers/proton-pump inhibitors, age, obesity, smoking and platelet microRNAs), decreased miR-223 expression was the only independent predictor associated with the presence of PRI-determined low responders to clopidogrel (OR 0.189, 95% CI 0.043 to 0.836, P = 0.028).

CONCLUSIONS:

The present work identifies decreased platelet miR-223 expression as a novel mechanism involved in blunted platelet response to clopidogrel in a Chinese population.

PMID:
23498169
DOI:
10.1016/j.thromres.2013.02.015
[Indexed for MEDLINE]
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