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Abstract
Coronary artery disease (CAD) and acute myocardial infarction (AMI) are the leading causes of death worldwide. Since only a subset of CAD patients develops myocardial infarction, it is likely that unique factors predispose to AMI. Circulating microRNAs represent diagnostic powerful biomarkers for detection of heart injuries and patients’ risk stratification. Using an array-based approach, the expression of 84 circulating miRNAs was analyzed in plasma of pooled stable CAD patients (CAD; n = 5) and unstable CAD patients (AMI_T0; n = 5) enrolled within 24 hours from an AMI event. The array experiments showed 27 miRNAs differentially expressed with a two-fold up- or down-regulation (10 up- and 17 down-regulated miRNAs). Among them, miR-423-5p dis-regulation was confirmed in a larger case study (n = 99). Circulating miR-423-5p resulted to be significantly down-regulated within 24 hours from the AMI event (FC = -2, p≤0.05). Interestingly, miR-423-5p expression resulted to be increased (FC = +2; p≤0.005) in a subgroup of the same AMI patients (AMI_T1; n = 11) analyzed after 6 months from the acute event. We extended miR-423-5p expression study on PBMCs (peripheral blood mononuclear cells), confirming also in this tissue its up-regulation at 6 months post-AMI. Receiver operating characteristic analyses (ROC) were performed to detect the power of miR-423-5p to discriminate stable and unstable CAD. In plasma, miR-423-5p expression accurately distinguishes stable and unstable CAD patients (AUC = 0.7143, p≤0.005). Interestingly, the highest discriminatory value (AUC = 0.8529 p≤0.0005) was identified in blood cells, where miR-423-5p expression is able to differentiate unstable CAD patients during an acute event (AMI_T0) from those at six months post-AMI (AMI_T1). Furthermore, cellular miR-423-5p may discriminate also stable CAD patients from unstable CAD patients after six months post-AMI (AUC = 0.7355 p≤0.05). The results of this pilot-study suggest that miR-423-5p expression level both in plasma and blood cells, could represent a new promising biomarker for risk stratification of CAD patients.
Highlights
Coronary artery disease (CAD) refers to the progressive development of atherosclerotic plaques in blood vessels and represents one of the leading causes of morbidity and mortality worldwide
Aim of this study is the identification of epigenetic biomarkers useful for the discrimination of patients with stable and unstable CAD, so we focused our analysis only on subjects already affected by coronary atherosclerosis
Primary percutaneous coronary intervention (PCI) was the first procedure for treating the culprit lesion in acute myocardial infarction (AMI) group; any other hemodynamically significant lesions were treated during the same procedure or in a staged coronary intervention
Summary
Coronary artery disease (CAD) refers to the progressive development of atherosclerotic plaques in blood vessels and represents one of the leading causes of morbidity and mortality worldwide. Atherosclerosis is a complex process that begins with endothelial cells dysfunction in the coronary arteries and can lead to a narrowing of the vessels obstructing the blood flow to the heart and causing acute myocardial infarction (AMI) [1,2,3]. Even if numerous studies investigated the pathogenesis of atherosclerosis and the development of ischemic heart disease, the mechanisms that regulate plaque stability, determining which subgroup of patients is more prone to develop acute coronary syndrome, are not yet completely understood [4,5]. Epigenetic modifications represent a key for a better understanding of the complex background of cardiovascular diseases and a new field of investigation for the discovery of new biomarkers with diagnostic and prognostic purposes [6]
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