High miR-124-3p expression identifies smoking individuals susceptible to atherosclerosis

作者：de Ronde Maurice W J; Kok Maayke G M; Moerland Perry D; Van den Bossche Jan; Neele Annette E; Halliani Amalia; Van der Made Ingeborg; de Winther Menno P J; Meijers Joost C M; Creemers Esther E; Pinto Sietsma Sara Joan^*

来源：Atherosclerosis, 2017, 263: 377-384.

DOI：10.1016/j.atherosclerosis.2017.03.045

• Smoking
• miR
• Atherosclerosis
• Monocytes

Background and aims: 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.
Methods: 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).
Results: 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 >= 80th percentile, cohort III n = 138) (OR 2.71, 95% CI 1.05e7.01). 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.
Conclusions: 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.

• 出版日期2017-8