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In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
MicroRNA-19b functions as potential anti-thrombotic protector in patients with unstable angina by targeting tissue
Sufang Li1, Jingyi Ren1, Ning Xu2
1Department of Cardiology, Peking University People's Hospital, Beijing, China.
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.
Insights
MicroRNAs (miRNAs) regulate hemostatic proteins. In unstable angina (UA) patients, elevated miR-19b in endothelial microparticles (EMPs) may inhibit tissue factor (TF), suggesting an anti-thrombotic role.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Hemostasis Research
Background:
- Hemostatic system activation is crucial in acute coronary events.
- MicroRNAs (miRNAs) are implicated in regulating hemostatic proteins.
- Microparticles (MPs) are key carriers of circulating miRNAs.
Purpose of the Study:
- To investigate the role of miRNAs in regulating hemostatic gene expression in unstable angina (UA) patients.
- To identify specific miRNAs involved in the hemostatic system in UA.
- To explore the relationship between miRNAs, microparticles, and endothelial dysfunction in UA.
Main Methods:
- MiRNA expression profiling in plasma from UA patients and controls.
- Real-time PCR validation of miRNA levels in plasma and plasma MPs.
- Flow cytometry to quantify plasma endothelial microparticles (EMPs).
- In vitro studies using cultured endothelial cells (ECs) to assess miR-19b release and TF regulation.
- Bioinformatics and luciferase reporter assays to confirm miR-19b targeting of TF mRNA.
Main Results:
- miR-19b was identified as a significantly differentially expressed miRNA in UA patients.
- Plasma EMP levels were elevated in UA patients.
- TNF-α stimulation increased miR-19b release and expression in ECs.
- miR-19b directly targets Tissue Factor (TF) mRNA.
- Overexpression of miR-19b inhibited TF expression and procoagulant activity in ECs.
Conclusions:
- Elevated miR-19b in EMPs of UA patients, linked to endothelial dysfunction, may contribute to increased circulating miR-19b.
- miR-19b potentially exerts an anti-thrombotic effect by inhibiting TF expression in endothelial cells.
- These findings highlight a novel miRNA-mediated regulatory mechanism in the hemostatic system of UA.
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