Abstract 9724: Microrna Expression in Circulating Microvesicles Predicts Cardiovascular Events in Patients With Coronary Artery Disease
Background: Circulating microRNAs (miRs) are differentially regulated and selectively packaged in microvesicles.
Hypothesis: Circulating vascular and endothelial miRs in patients with stable coronary artery disease (CAD) have prognostic impact on the occurrence of cardiovascular events.
Methods and Results: Ten miRs involved in the regulation of vascular performance including miR-126, miR-222, miR-let 7d, miR-21, miR-20a, miR-27a, miR-92a, miR-17, miR-130 and miR-199a were quantified in plasma and circulating microvesicles (MVs) by RT-PCR in 181 stable CAD patients. The median follow-up time for major adverse cardiovascular event (MACE)-free survival was 6.1 (6.0/6.4) years. Events occurred in 55 (31.3%) patients. There was no significant association between cardiovascular events and plasma level of analysed miRs. In contrast, increased expression of miR-126 and miR-199a in circulating MVs (MmiR) was significantly associated with a lower MACE rate. In multivariate analysis, levels of MmiR-126 above the median were predictors of MACE-free survival (hazard ratio: 0.381, 95% CI: 0.190-0.764; P=0.007) and revascularization (hazard ratio: 0.391, 95% CI: 0.178-0.861; P=0.02). Likewise, an increased level of MmiR-199a was associated with a reduced risk of MACE (hazard ratio: 0.414, 95% CI: 0.211-0.812; P=0.01) and revascularization rate (hazard ratio: 0.305, 95% CI: 0.135-0.691; P=0.004) in multivariate analysis. miR expression analysis in plasma compartments (exosomes, microparticles, vesicles-free supernatant) revealed that miR-126 and miR-199a are mainly present in circulating microparticles. In vitro, endothelial cells were found to be the major cell source of miR-126- and miR-199a-containing MVs.
Conclusion: Expression of microvesicle-incorporated miR-126 and miR-199a but not freely circulating miRs predicts the occurrence of cardiovascular events in stable CAD patients.
Author Disclosures: F. Jansen: None. X. Yang: None. J.M. Sinning: None. G. Nickenig: None. N. Werner: None.
- © 2014 by American Heart Association, Inc.