Diagnostic Potential of Plasmatic MicroRNA Signatures in Stable and Unstable Angina

Abstract

PurposeWe examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina.MethodsAn exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated.ResultsOut of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA.ConclusionsThis work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.

microRNAs in cardiovascular disease – clinical application

“…Similar results were reported when a set of microparticle-derived pro-inflammatory miRNAs from plasma of 10 patients was observed to discriminate between SAP and UAP [90]. Although a similar approach could not validate these results [26], promising results were reported in a clinical screening-validation setting comprising 46 UAP patients compared with 63 NCCP patients [37]. The authors found a miRNA signature consisting of miR-132, miR-150, and miR-186, which strongly discriminated UAP and NCCP [37].…”

State of the Art: Blood Biomarkers for Risk Stratification in Patients with Stable Ischemic Heart Disease

“…So far more than 2000 human miRs have been identified and some have been associated with the development of disease including cardiovascular disease. Although investigators have reported that specific plasmatic miR signatures appear to be associated with stable or unstable IHD, the ability to distinguish between stable and unstable disease seems limited (62 ). Moreover, limited data have been available concerning the prognostic value in stable IHD (63 ), but a recent report suggests that miR-132, miR-140 -3p, and miR-210 may predict death in patients with ACS (64 ).…”

Plasmatic MicroRNA Signatures in Elderly People with Stable and Unstable Angina

“…1) Among these patients, 50% are due to acute coronary syndrome (ACS), including stable angina (SA), unstable angina (UA), and myocardial infarction. 2) Myocardial infarction can be diagnosed by the elevated plasmatic levels of cardiac-specific protein troponin. However, there are no established circulating biomarkers that may distinguish SA and UA currently, and the latter, as a kind of ACS, is more likely to develop into myocardial infarction and result in an increase in mortality.…”