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

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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 1.05-7.01). 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.

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.

Original languageEnglish
Pages (from-to)377-384
Number of pages8
JournalAtherosclerosis
Volume263
DOIs
Publication statusPublished - Aug 2017

Cite this

de Ronde, M. W. J., Kok, M. G. M., Moerland, P. D., Van den Bossche, J., Neele, A. E., Halliani, A., ... Pinto-Sietsma, S-J. (2017). High miR-124-3p expression identifies smoking individuals susceptible to atherosclerosis. Atherosclerosis, 263, 377-384. https://doi.org/10.1016/j.atherosclerosis.2017.03.045