title: Decreased circulating microRNA-223 level predicts high on-treatment platelet reactivity in patients with troponin-negative non-ST elevation acute coronary syndrome.
abstract: To investigate the relationship between circulating microRNA 223 (miR-223) levels and clopidogrel responsiveness in patients with coronary heart disease. A total of 62 consecutive patients with troponin-negative non-ST elevation acute coronary syndrome (NSTE-ACS) scheduled for elective percutaneous coronary intervention were enrolled. The plasma circulating miR-223 levels were quantified by real-time PCR, and platelet reactivity was determined by platelet reactivity index (PRI), measured by vasodilator-stimulated phosphoprotein (VASP) phosphorylation flow cytometry after 300 mg (for at least 24 h) or 75 mg clopidogel (for at least 5 days) plus aspirin treatment. All subjects were dichotomized according to PRI median (normal-responders: PRI ≤ 56.3%, n = 31 and low-responders: PRI > 56.3%, n = 31). Compared with normal-responders, circulating miR-223 level was significantly decreased in low-responders (P = 0.007). In addition, miR-223 level was statistically correlated with PRI (Spearman r = -0.379, P = 0.002). Stepwise binary logistic regression analysis revealed that among factors that potentially influence platelet reactivity (CYP2C19*2/*3 loss-of-function genotypes, use of calcium channel blockers/proton-pump inhibitors, age, diabetes and smoking), decreased circulating miR-223 level was the only independent predictor for the presence of PRI-determined lower responders (OR 0.111, 95% CI 0.018-0.692, P = 0.019). Our data suggest that circulating miR-223 may serve as a novel biomarker for assessment of clopidogrel responsiveness in troponin-negative NSTE-ACS patients.
authors.affiliation: Graduate School of Medicine, Tianjin Medical University, Tianjin, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Ji
authors.forename: Rui
authors.initials: R
authors.lastname: Shi
authors.forename: Rui-Yi
authors.initials: RY
authors.lastname: Lu
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Li
authors.forename: Guo-Hong
authors.initials: GH
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.forename: Jian-Qi
authors.initials: JQ
authors.lastname: Zhang
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Zhao
authors.forename: Tie-Min
authors.initials: TM
authors.lastname: Jiang
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Li
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014336:Troponin / Q000235:genetics / Q000378:metabolism
chemical_list: D001241:Aspirin; D015415:Biomarkers; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D035683:MicroRNAs; D010975:Platelet Aggregation Inhibitors; D013988:Ticlopidine; D014336:Troponin; C525067:MIR223, human; C045793:CYP2C19 protein, human