[Statins decreases expression of five inflammation-associated microRNAs in the plasma of patients with unstable angina].

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.

High density lipoprotein suppresses lipoprotein associated phospholipase A2 in human monocytes-derived macrophages through peroxisome proliferator-activated receptor-γ pathway.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is mainly secreted by macrophages, serving as a specific marker of atherosclerotic plaque and exerting pro-atherogenic effects. It is known that high-density lipoprotein (HDL) plays an important role against atherosclerosis by inhibiting pro-inflammatory factors, however, the relationship between HDL and Lp-PLA2 remains elusive. METHODS: In this study, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and a platelet-activating factor (PAF) acetylhydrolase assay were performed to determine the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages upon HDL treatment of different concentrations and durations. To investigate the underlying mechanism of HDL-induced Lp-PLA2 action, pioglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ) ligand, was introduced to human monocyte-derived macrophages and mRNA and protein levels of Lp-PLA2, as well as its activity, were determined. RESULTS: Lp-PLA2 mRNA levels, protein expression and activity were significantly inhibited in response to HDL treatment in a dose and time dependent manner in human monocyte-derived macrophages. Pioglitazone treatment (1 - 10 ng/ml) upregulated the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages, while the effects were markedly reversed by HDL. In addition, pioglitazone resulted in a significant increase in PPARγ phosphorylation in human monocyte-derived macrophages, which could be inhibited by HDL. CONCLUSION: These findings indicate that HDL suppresses the expression and activity of Lp-PLA2 in human monocyte-derived macrophages, and the underlying mechanisms may be mediated through the PPARγ pathway.