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.
Highlights
The amount of patients hospitalized in Western countries for chest pain accounts for several millions each year
In a more recent work, we have shown that circulating miR-499-5p may be a useful marker for early discrimination between congestive heart failure and Non STElevation Myocardial Infarction (NSTEMI) in elderly patients presenting to hospital with unclear symptoms [9]
In the search for diagnostic biomarkers of chest pain of cardiac origin, circulating miRNAs have been previously investigated in blood, serum, plasma, platelets, and peripheral blood mononuclear cells (PBMC) in patients with both stable and unstable angina [10]
Summary
The amount of patients hospitalized in Western countries for chest pain accounts for several millions each year. In approximately half of the cases, chest pain is of cardiac origin [1]. Among these patients, approximately 50% exhibit an underlying coronary artery disease (CAD), causing either stable (SA) or unstable (UA) angina pectoris or myocardial infarction. In the absence of myocardial necrosis leading to increased plasmatic levels of the cardiac-specific protein Troponin, there are currently no established circulating biomarkers that may support the diagnosis of SA or UA. Missed diagnosis of cardiac ischemia has been demonstrated to cause an increase in early and mid-term mortality [2]. The identification of novel noninvasive biomarkers of CAD lacking myocardial necrosis is a compelling need still under investigation
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