Decreased miR-181a Expression in Monocytes of Obese Patients Is Associated with the Occurrence of Metabolic Syndrome and Coronary Artery Disease
Decreased miR-181a Expression in Monocytes of Obese Patients Is Associated with the Occurrence of Metabolic Syndrome and Coronary Artery Disease
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DOI：
10.1210/jc.2012-1008
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发表时间：
2012-07-01
影响因子：
5.8
通讯作者：
Holvoet, Paul
中科院分区：
文献类型：
--
作者：
Hulsmans, Maarten;Sinnaeve, Peter;Holvoet, Paul
背景：肥胖期间的炎症与代谢综合征和冠状动脉疾病(CAD)的高风险相关。单核细胞中炎性Toll样受体(TLR)/核因子-kappaB(NF-kappa B)信号的激活参与了炎症的发生。减肥手术后的体重减轻导致肥胖相关并发症的显著改善。MicroRNA(MiR)，一类小的非编码RNA，被认为是炎症过程的负调控因子。目的：本研究试图确定肥胖患者单核细胞中miR的异常与TLR/NF-kappa B信号、代谢综合征和冠心病相关。设计、背景和患者：这项回顾性研究包括两个独立的队列，21名病态肥胖患者和125名高危肥胖和非肥胖患者。干预：包括减肥手术(n=21)，随访3个月。主要观察指标：通过微阵列分析CD14(+)单核细胞MIR的表达。TLR/NFkappa B相关的miR通过电子靶点预测分析确定。定量RT-PCR检测其表达情况。结果：MIR-181a、-181b和-181d可能是TLR/NF-kappa B信号的调节因子，肥胖单核细胞中MIR-181a、-181b和-181d的表达减少，体重减轻使它们的表达正常化到瘦肉者单核细胞中的水平。即使在调整了传统危险因素、肥胖和代谢综合征后，miR-181a而不是miR-181b和miR-181d与更多的代谢综合征成分和CAD相关。结论：本研究证实肥胖患者单核细胞中与TLR/NF-kappa B相关的miR-181a表达下调，提示它可能是代谢综合征和CAD的生物标志物。(J临床内分泌Metab 97：E1213-E1218,2012)
Context: Inflammation during obesity is associated with higher risk of metabolic syndrome and coronary artery disease (CAD). Activation of the inflammatory toll-like receptor (TLR)/nuclear factor kappa B (NF kappa B) signaling in monocytes contributes to inflammation. Weight loss after bariatric surgery leads to significant improvement of obesity-related comorbidities. MicroRNA (miR), a class of small noncoding RNA, have been implicated as negative regulators of inflammatory processes.Objective: This study sought to identify dysregulated miR in monocytes of obese patients associated with TLR/NF kappa B signaling, metabolic syndrome, and CAD.Design, Setting, and Patients: This retrospective study included two independent cohorts of 21 morbidly obese and 125 high-risk obese and nonobese patients in a hospitalized care setting.Intervention: Intervention included bariatric surgery (n = 21) with a 3-month follow-up.Main Outcome Measures: miR expressions in CD14(+) monocytes were determined by microarray analysis. TLR/NF kappa B-related miR were identified by an in silico target prediction analysis. Their expression was validated by quantitative RT-PCR. Their association with metabolic syndrome and angiographically documented CAD was assessed.Results: miR-181a, -181b, and -181d, identified as possible regulators of the TLR/NF kappa B signaling, were decreased in obese monocytes, and weight loss normalized their expression to levels observed in monocytes of lean persons. miR-181a but not miR-181b and miR-181d was associated with a higher number of metabolic syndrome components and with CAD even after adjustment for traditional risk factors, obesity and the metabolic syndrome.Conclusion: This study demonstrates that the TLR/NF kappa B-related miR-181a is down-regulated in monocytes of obese patients and suggests that it is a putative biomarker of metabolic syndrome and CAD. (J Clin Endocrinol Metab 97: E1213-E1218, 2012)