MicroRNA-150

Abstract

Background-Left ventricular (LV) remodeling after acute myocardial infarction is associated with adverse prognosis.MicroRNAs (miRNAs) regulate the expression of several genes involved in LV remodeling. Our aim was to identify miRNAs associated with LV remodeling after acute myocardial infarction. Methods and Results-We studied 90 patients after first ST-segment-elevation acute myocardial infarction. A derivation cohort consisted of 60 patients characterized by echocardiography predischarge and at 6-month follow-up. Thirty patients characterized by magnetic resonance imaging predischarge and at 4-month follow-up were the validation cohort. Remodeling was defined as an increase in LV end-diastolic volume (ΔEDV>0) between discharge and follow-up. Circulating miRNAs were measured by microarrays and polymerase chain reaction. Using a systems-based approach, we identified several miRNAs potentially involved in LV remodeling. In the derivation cohort, one of these miRNAs, miR-150, was downregulated in patients with remodeling (ΔEDV>0) compared with patients without remodeling (ΔEDV≤0). In the validation cohort, patients with remodeling had 2-fold lower levels of miR-150 than those without (P=0.03). miR-150 outperformed N-terminal pro-brain natriuretic peptide to predict remodeling (area under the receiver-operating characteristic curve of 0.74 and 0.60, respectively). miR-150 reclassified 54% (95% confidence interval, 5-102; P=0.03) of patients misclassified by N-terminal pro-brain natriuretic peptide and 59% (95% confidence interval, 9-108; P=0.02) of patients misclassified by a multiparameter clinical model, including age, sex, and admission levels of troponin I, creatine kinase, and N-terminal pro-brain natriuretic peptide. hypertrophic heart 10-13 and in the circulation of patients with heart failure. Conclusions-Low14 Because miRNAs play functional roles in the development of heart failure, 15 modulation of their expression and activity has emerged as an attractive potential tool to limit the development of this condition. However, the prognostic value of miRNAs after AMI has received less attention.In a study by Widera et al, 16 circulating levels of 6 cardiacenriched miRNAs were measured in patients with acute coronary syndrome. Levels of miR-133a and miR-208b were upregulated in patients with AMI (compared with patients with unstable angina) and were associated with the risk of death. However, this association was lost after adjustment for high-sensitivity cardiac troponin T. Interestingly, circulating miRNAs follow a typical expression profile post-AMI that may be used for prognostic purposes.17 For instance, miR-208a increased 5 days post-AMI and remained elevated up to 90 days later. In a recent study evaluating the diagnostic value of circulating miRNAs in patients with AMI, we observed a weak association between cardiac-enriched miR-208b and miR-499 and LV dysfunction. 18Using a systems-based approach, combining analyses of miRNA profiles, obtained by microarrays, with networks of miRNA gene interactions, ...

Left Ventricular Remodeling after Acute Myocardial Infarction and Biomarkers

“…In a study by Devaux et al [25], low levels of miR-150 are associated with LV remodeling after the first ST-AMI. According to Devaux et al [26], low levels of miR-150, miR-101 or elevated levels of miR-16 and miR-27a were at increased risk of impaired LV contractility and were involved in cardiac remodeling after MI.…”

MicroRNAs; easy and potent targets in optimizing therapeutic methods in reparative angiogenesis

“…The most shared miRNAs are endothelial cell (EC) derived and include miR‐126/17–92/15/34 clusters as representing highly circulating miRNAs 2, 3, 4, 5, 6.…”

“…Thus, EC dysfunction and ageing‐related degenerative problems lie, at least in part, within the tissue‐specific released miRNAs 6, 15, 29, 50, 51, 80.…”

European Perspectives

“…2,3 Recently, they identified a novel microRNA, miR-150, able to predict the development of left ventricular remodelling after acute myocardial infarction. 4 Dr Devaux says, "Active participation in the GREAT network on acute clinical conditions, gathering >200 members from 30 countries worldwide, is a springboard for the research performed at Centre de Recherche Public de la Santé on cardiac microRNAs. "…”