Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Atherosclerosis. 2017 Aug;263:377-384. doi: 10.1016/j.atherosclerosis.2017.03.045. Epub 2017 Apr 5.
The risk of developing cardiovascular disease (CVD) is twice as high among smoking individuals compared to non-smokers. Monocytes are involved in smoking-related atherosclerotic plaque formation. In this study, we investigated whether smokers with an increased risk of developing CVD can be identified on the basis of monocyte-derived miRNA expression levels.
We performed a miRNA microarray experiment on isolated monocytes from smoking, former smoking and non-smoking individuals in a cohort of patients with premature CVD and healthy controls (Cohort I, n = 76).
We found miR-124-3p to be heterogeneously expressed among all smoking individuals, whereas expression was low in non-smokers. Subsequently, RT-qPCR measurements on whole blood showed that among smoking individuals an increase in miR-124-3p is associated with an increased risk for advanced atherosclerotic disease (cohort II, n = 24) (OR 11.72 95% CI 1.09-126.53) and subclinical atherosclerosis (coronary artery calcium score ≥ 80 percentile, cohort III n = 138) (OR 2.71, 95% CI 1.05-7.01). This was not observed among former smokers or non-smoking individuals. Flow cytometric analysis demonstrated that high miR-124-3p expression was associated with upregulation of the monocyte surface markers CD45RA, CD29 and CD206, indicating an altered monocyte phenotype. Finally, overexpression of miR-124-3p resulted in an upregulation of CD206 surface expression on monocytes.
High miR-124-3p expression is associated with an increased risk of subclinical atherosclerosis in smoking individuals and with an altered monocyte phenotype. This may suggest that miR-124-3p identifies which smoking individuals are susceptible to the atherogenic effects of smoking.
与非吸烟者相比，吸烟人群发生心血管疾病（CVD）的风险高两倍。单核细胞参与了与吸烟相关的动脉粥样硬化斑块形成。在本研究中，我们研究了是否可以根据单核细胞衍生的 miRNA 表达水平来识别那些具有 CVD 发病高风险的吸烟者。
我们对来自于 CVD 发病提前的患者和健康对照者队列（队列 I，n=76）中分离的吸烟、曾经吸烟和非吸烟个体的单核细胞进行了 miRNA 微阵列实验。
我们发现所有吸烟个体的 miR-124-3p 表达存在异质性，而非吸烟者的表达水平较低。随后，对全血的 RT-qPCR 测量表明，在吸烟个体中，miR-124-3p 的增加与进展性动脉粥样硬化疾病的风险增加相关（队列 II，n=24）（OR 11.72 95%CI 1.09-126.53）和亚临床动脉粥样硬化（冠状动脉钙评分≥80 百分位数，队列 III，n=138）（OR 2.71，95%CI 1.05-7.01）。在曾经吸烟者或非吸烟者中未观察到这种情况。流式细胞术分析表明，高 miR-124-3p 表达与单核细胞表面标志物 CD45RA、CD29 和 CD206 的上调相关，表明单核细胞表型发生改变。最后，miR-124-3p 的过表达导致单核细胞表面 CD206 表达的上调。
高 miR-124-3p 表达与吸烟个体的亚临床动脉粥样硬化发病风险增加以及单核细胞表型改变相关。这可能表明 miR-124-3p 可识别出哪些吸烟个体易受吸烟的致动脉粥样硬化作用影响。
