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 language | English |
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Pages (from-to) | 377-384 |
Number of pages | 8 |
Journal | Atherosclerosis |
Volume | 263 |
Early online date | 2017 |
DOIs | |
Publication status | Published - Aug 2017 |
Keywords
- Adult
- Atherosclerosis/blood
- 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
- Middle Aged
- Monocytes/metabolism
- Odds Ratio
- Oligonucleotide Array Sequence Analysis
- Phenotype
- Receptors, Cell Surface/blood
- Reverse Transcriptase Polymerase Chain Reaction
- Risk Factors
- Smoking/adverse effects
- Up-Regulation