Key result
In patients with unstable angina, miR-155 was the most upregulated of 451 differentially expressed microRNAs in CD4+ T cells, promoting Th1 dominance by repressing IFN-γ Rα.
Case-Control (n=84)
Upregulation of miR-155 in CD4+ T cells of patients with unstable angina promotes a Th1 bias by repressing IFN-γ Rα, potentially enhancing plaque instability.
MiR-155 may associate with Th1 imbalance in unstable angina; hypothesis-generating and should not yet change practice.
An imbalance between T helper 1 (Th1) and T helper 2 (Th2) cells has been reported to increase plaque instability in patients with unstable angina (UA). MicroRNAs play a vital role in the differentiation of CD4(+) T cells. However, the role of microRNAs in regulation of Th1/Th2 balance in UA remains unclear. In this study, we aimed to elucidate microRNA expression profiles of circulating CD4(+) T cells in UA and to explore the function of microRNAs in the Th1/Th2 balance. A total of 53 patients with UA and 31 control subjects without coronary artery disease were enrolled. Microarray analysis of the microRNA expression profiles of CD4(+) T cells revealed that miR-155 was the most significantly upregulated microRNA of the 451 differentially expressed microRNAs. The upregulation of miR-155 expression was positively correlated with the percentage of Th1 cells and interferon-gamma (IFN-γ) levels in patients with UA. In addition, overexpression of miR-155 in human circulating CD4(+) T cells promoted Th1 differentiation. Further studies identified IFN-γ receptor alpha chain (IFN-γ Rα) mRNA as a direct and functional target of miR-155. A luciferase reporter assay verified that miR-155 directly targeted IFN-γ Rα mRNA. Small-interfering RNA-mediated knockdown of IFN-γ Rα mRNA showed effects similar to those of ectopic miR-155 expression. Thus, our study indicated that upregulation of miR-155 in circulating CD4(+) T cells in patients with UA promoted a shift in the Th1/Th2 balance toward Th1 dominance by repressing IFN-γ Rα, which may subsequently enhance plaque instability.
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Chen et al. (2015) conducted a case-control in Unstable angina (n=84). Unstable angina vs. Control subjects without coronary artery disease was evaluated on microRNA expression profiles of circulating CD4(+) T cells and Th1/Th2 balance. In patients with unstable angina, miR-155 was the most upregulated of 451 differentially expressed microRNAs in CD4+ T cells, promoting Th1 dominance by repressing IFN-γ Rα.
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