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

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 de...

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Bibliographic Details
Published in:Atherosclerosis 2017-08, Vol.263, p.377-384
Main Authors: 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
Format: Article
Language:English
Subjects:
Adult
Atherosclerosis
Atherosclerosis - blood
Atherosclerosis - diagnosis
Atherosclerosis - genetics
Cardiovascular
Case-Control Studies
Female
Flow Cytometry
Genetic Markers
Genetic Predisposition to Disease
Humans
Integrin beta1 - blood
Lectins, C-Type - blood
Leukocyte Common Antigens - blood
Logistic Models
Male
Mannose-Binding Lectins - blood
MicroRNAs - blood
MicroRNAs - genetics
Middle Aged
miR
Monocytes
Monocytes - metabolism
Odds Ratio
Oligonucleotide Array Sequence Analysis
Phenotype
Receptors, Cell Surface - blood
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors
Smoking
Smoking - adverse effects
Smoking - blood
Smoking - genetics
Up-Regulation
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Summary: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 for the atherogenic effects of smoking.
ISSN:0021-9150
1879-1484
DOI:10.1016/j.atherosclerosis.2017.03.045