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Third universal definition of myocardial infarction. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Is Coronary Atherosclerosis One Disease or Many? Setting Realistic Expectations for Precision Medicine. Progress and challenges in translating the biology of atherosclerosis. 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. 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). 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).
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In plasma, miR-423-5p expression accurately distinguishes stable and unstable CAD patients (AUC = 0.7143, p≤0.005). Receiver operating characteristic analyses (ROC) were performed to detect the power of miR-423-5p to discriminate stable and unstable CAD. 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. 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. Circulating miR-423-5p resulted to be significantly down-regulated within 24 hours from the AMI event (FC = -2, p≤0.05). Among them, miR-423-5p dis-regulation was confirmed in a larger case study (n = 99). The array experiments showed 27 miRNAs differentially expressed with a two-fold up- or down-regulation (10 up- and 17 down-regulated miRNAs). 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.
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Circulating microRNAs represent diagnostic powerful biomarkers for detection of heart injuries and patients' risk stratification. Since only a subset of CAD patients develops myocardial infarction, it is likely that unique factors predispose to AMI. Coronary artery disease (CAD) and acute myocardial infarction (AMI) are the leading causes of death worldwide.
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