title: MicroRNA-19b functions as potential anti-thrombotic protector in patients with unstable angina by targeting tissue factor.
abstract: The activation of a hemostatic system plays a critical role in the incidence of acute coronary events. Hemostatic proteins may be regulated by microRNAs (miRNAs). Microparticles (MPs) are the major carrier of circulating miRNAs. The aim of this study was to determine the potential role of miRNAs in regulating gene expression involved in the hemostatic system in patients with unstable angina (UA). MiRNA expression profiles in the plasma from patients with UA (UA group, n=9) compared with individuals with clinical suspicion of coronary artery disease (CAD) but negative angiography (control group, n=9) showed that among 36 differentially expressed miRNAs, miR-19b was the most obvious one. Using real-time PCR, 5 selected miRNA levels in plasma (UA group, n=20; control group, n=30) and plasma MPs (UA group n=6; control group n=6) were proved to be consistent with the miRNA array. Flow cytometry analysis indicated that the amounts of plasma endothelial microparticles (EMPs) were increased in UA patients (UA group, n=4) compared to controls (control group, n=4). In cultured endothelial cells (ECs), TNF-α increased miR-19b release and expression. Tissue factor (TF) was predicted to be the target of miR-19b by bioinformatics analysis. Luciferase reporter assays demonstrated that miR-19b binds to TF mRNA. Overexpression of miR-19b inhibited TF expression and procoagulant activity. This study indicates that in UA patients, the increase of miR-19b wrapped in EMPs due to endothelial dysfunction may partially contribute to the circulating miR-19b elevation and miR-19b may play an anti-thrombotic role by inhibiting the expression of TF in ECs.
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Geng
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China.
authors.forename: Chengfu
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China.
authors.forename: Chongyou
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China.
authors.forename: Junxian
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China.
authors.forename: Jingjin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China. Electronic address: chenhongbj@medmail.com.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D000789:Angina, Unstable / Q000097:blood / Q000235:genetics*; D000991:Antithrombins / Q000097:blood / Q000378:metabolism*; D001483:Base Sequence; D001777:Blood Coagulation / Q000187:drug effects; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism; D015331:Cohort Studies; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D015203:Reproducibility of Results; D013925:Thromboplastin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000991:Antithrombins; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin
keywords: Endothelial cells; Microparticles; Thrombosis; Tissue factor; Unstable angina; miRNAs