网络出版日期: 2015-10-18
基金资助
国家自然科学基金项目(81270274)和“重大新药创制”国家科技重大专项(2012ZX09303019)资助
Statins decreases expression of five inflammation-associated microRNAs in the plasma of patients with unstable angina
Online published: 2015-10-18
Supported by
Supported by the National Natural Science Foundation of China (81270274) and Major Project of National Science and Technology “Creation of Major New Drugs” (2012ZX09303019).
目的:评估服用他汀类药物对不稳定性心绞痛患者血浆中microRNAs(miRNAs)表达谱的影响。方法:采用miRNAs TLDA(Taqman lowdensity array)芯片对长期规律服用他汀类药物的不稳定性心绞痛患者(他汀治疗组,n=6)及未曾服用过他汀类药物的不稳定性心绞痛患者(非他汀治疗组,n=6)血浆中差异表达的miRNAs表达谱进行筛查,并选择部分差异表达的炎症相关的miRNAs在非心源性胸痛患者(对照组,n=20)、未曾服用过他汀类药物的不稳定性心绞痛患者(非他汀治疗组,n=26)、长期规律服用他汀类药物的不稳定性心绞痛患者(他汀治疗组,n=19)中采用real-time PCR的方法进行验证。结果: 他汀治疗组患者血浆中miRNAs的表达谱与非他汀治疗组患者相比差异有统计学意义,包括miR-106b、miR-21、miR-25、miR-451以及 miR92a等炎症相关miRNAs在内的21种血浆miRNAs水平显著降低(组间差异倍数>3,错误发现率<0.0001%),选取miR106b、miR21、miR25、miR451以及 miR92a进行real-time PCR验证的结果与芯片筛查结果一致,与未曾服用过他汀类药物的患者相比,长期规律服用他汀类药物可降低上述5种炎症相关miRNAs的表达水平(P<0.05),而非他汀治疗组患者血浆中上述5种炎症相关miRNAs的表达水平高于对照组(P<0.001)。结论:服用他汀类药物可显著降低不稳定性心绞痛患者血浆中一组炎症相关的miRNAs的表达水平。
张静 , 任景怡 , 陈红 , 韩冠平 . 他汀类药物可降低不稳定性心绞痛患者血浆中炎症相关microRNAs的表达水平[J]. 北京大学学报(医学版), 2015 , 47(5) : 761 -768 . DOI: 10.3969/j.issn.1671-167X.2015.05.006
Objective:To explore the influence of treatment with HMG-CoA reductase inhibitors (sta-tins) 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.
Key words: Angina, unstable; MicroRNAs; Statins; Plasma
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