OBJECTIVE: To explore the influence of treatment with HMG-CoA reductase inhibitors (statins) on the expression profile of microRNAs (miRNAs) in the plasma of patients with unstable angina (UA). METHODS: The Taqman low-density miRNA array (TLDA) and significance analysis of microarrays (SAM) were used to identify distinct miRNA expression profiles in the plasma of UA patients treated with long-term and regular statins (UA receiving statins, n=6) compared with UA patients who had not received statins therapy before (UA received no statins, n=6). These differentially expressed miRNAs discovered in the profiling were further validated by real-time PCR in another 20 controls with non-cardiac chest pain, 26 UA patients received no statins, and 19 UA patients received statins. RESULTS: By using TLDA and SAM, significantly decreased expression levels of 21 miRNAs were observed in the UA patients receiving statins compared with those who received no statins (fold change>3 and false discovery rate<0.0001%). The unsupervised hierarchical clustering based on miRNA expression clearly separated the UA patients receiving statins from those who received no statins. Consistent with the profiling data, the levels of 5 inflammation-associated miRNAs (miR-106b, miR-21, miR-25, miR-451, and miR-92a) were down regulated (P<0.05) in the UA patients receiving statins compared with those who received no statins. CONCLUSION: A group of inflammation-associated miRNAs, consisting of miR-106b, miR-21, miR-25, miR-451, and miR-92a, could be decreased by treatment with statins and may be used as a novel biomarker for effectiveness of statins therapy in patients with UA.