Abstract 12067: Circulating MicroRNAs Expression in Human Plasma is Dysregulated by Coronary Artery Disease
Purpose: Circulating miRNAs have been proposed as novel biomarkers of ischemic heart disease. We examined miRNAs expression profiles of patients with Stable (SA) and Unstable (UA) angina in comparison to matched controls.
Methods: 367 miRNAs were screened in plasma samples from healthy donors, SA and UA patients: miRNAs expression was evaluated using TaqMan Arrays followed by a validation step. We also investigated 14 additional miRNAs known to be regulated by CAD (miR-17, -92a, -126, -133a, -145, -155, -199a and -208a) and Myocardial Infarction (miR-1, -122, -133a, -133b, -375 and -499-5p). Selected miRNAs were examined in the plasma of healthy subjects (n=20) and Troponin-negative UA (n=19) and SA (n=34) patients, matched for age and cardiovascular risk factors.
Results: Of 178 miRNAs found stably expressed in all considered plasma samples, 3 showed positive modulation by CAD: miR-337-5p, miR-433, (9.4 and 9.6 folds, SA patients Vs controls) and miR-485-3p (42.4 and 29.7 folds, SA and UA patients Vs controls, respectively). In addition, miR-1, -126, -133a and miR-199a are positively modulated in both UA and SA patients. Further, miR-122 and -133b are up-regulated in SA patients only, while miR-145 in UA subjects only. No significant differences were found between SA and UA patients. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, -133b and 483-5p in SA patients Vs controls, while miR-1, -126 and -133a demonstrated a good ability to differentiate UA subjects from healthy subjects. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchic cluster analysis showed that the combination of miR-1, -133a and -126 and of miR-1 and -126 correctly classified respectively UA and SA patients Vs controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably classify patients when UA and SA were compared.
Conclusions: This work shows that specific plasmatic miRNA signatures have the potential to unveil with high efficiency the presence of angiographically documented Stable and Unstable CAD vs. matched healthy controls. We failed to produce evidences of plasmatic miRNAs capable to discriminate Stable from Unstable CAD patients.
- © 2013 by American Heart Association, Inc.