Statins inhibit cholesterol biogenesis and modulate atheroma inflammation to reduce cardiovascular risks. Promoted by immune and non-immune cells, serum C-reactive protein (CRP) might be a biomarker suboptimal to assess inflammation status. Although it has been reported that statins modulated inflammation via microRNAs (miRNAs), evidence remains lacking on comprehensive profiling of statin-induced miRNAome alterations in immune cells. We recruited 19 hypercholesterolemic patients receiving 2mg/day pitavastatin and 15 ones receiving 10mg/day atorvastatin treatment for 12 weeks, and performed microarray-based profiling of 1733 human mature miRNAs in peripheral blood mononuclear cells (PBMCs) before and after statin treatment. Differentially expressed miRNAs were determined if their fold changes were >1.50 or <0.67, after validated using quantitative polymerase chain reaction (qPCR). The miRSystem and miTALOS platforms were utilized for pathway analysis. Of the 34 patients aged 63.7±6.2 years, 27 were male and 19 were with coronary artery disease. We discovered that statins induced differential expressions of miR-483-5p, miR-4667-5p, miR-1244, and miR-3609, with qPCR-validated fold changes of 1.74 (95% confidence interval, 1.33 to 2.15), 1.61 (1.25 to 1.98), 1.61 (1.01 to 2.21), and 1.68 (1.19 to 2.17), respectively. The fold changes of the four miRNAs were not correlated with changes of low-density-lipoprotein cholesterol or CRP, after sex, age, and statin type were adjusted. We also revealed that RhoA and transforming growth factor-β signaling pathways might be regulated by the four miRNAs. Given our findings, miRNAs might be involved in statin-induced inflammation modulation in PBMCs, providing likelihood to assess and reduce inflammation in patients with atherosclerotic cardiovascular diseases.

中文翻译：

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他汀类药物诱导的 microRNAome 改变调节高胆固醇血症患者外周血单核细胞的炎症途径。


他汀类药物可抑制胆固醇生物发生并调节动脉粥样硬化炎症，从而降低心血管风险。在免疫和非免疫细胞的促进下，血清 C 反应蛋白 (CRP) 可能是评估炎症状态的次优生物标志物。尽管有报道称他汀类药物通过 microRNA (miRNA) 调节炎症，但仍缺乏对他汀类药物诱导的免疫细胞中 miRNA 组变化的全面分析的证据。我们招募了 19 名接受 2 毫克/天匹伐他汀治疗的高胆固醇血症患者和 15 名接受 10 毫克/天阿托伐他汀治疗 12 周的患者，并对他汀类药物治疗前后外周血单核细胞 (PBMC) 中的 1733 个人类成熟 miRNA 进行了基于微阵列的分析。使用定量聚合酶链式反应 (qPCR) 进行验证后，如果差异表达的 miRNA 倍数变化为 >1.50 或 <0.67，则确定差异表达的 miRNA。利用 miRSystem 和 miTALOS 平台进行通路分析。 34例患者中，年龄为63.7±6.2岁，其中27例为男性，19例患有冠状动脉疾病。我们发现他汀类药物诱导 miR-483-5p、miR-4667-5p、miR-1244 和 miR-3609 的差异表达，qPCR 验证的倍数变化为 1.74（95% 置信区间，1.33 至 2.15）、1.61（分别为 1.25 至 1.98）、1.61（1.01 至 2.21）和 1.68（1.19 至 2.17）。调整性别、年龄和他汀类药物类型后，4个miRNA的倍数变化与低密度脂蛋白胆固醇或CRP的变化不相关。我们还揭示了 RhoA 和转化生长因子-β 信号通路可能受这四种 miRNA 的调节。 鉴于我们的发现，miRNA 可能参与他汀类药物诱导的 PBMC 炎症调节，为评估和减少动脉粥样硬化性心血管疾病患者的炎症提供了可能性。