MicroRNA-150: A novel marker of left ventricular remodeling after acute myocardial infarction.
- Cardiovascular Research Unit
Background—Left ventricular (LV) remodeling after acute myocardial infarction (AMI) 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 AMI. Methods and Results—We studied 90 patients following first ST elevation AMI (STEMI). A derivation cohort consisted of 60 patients characterized by echocardiography pre-discharge and at 6 months follow-up. Thirty patients characterized by magnetic resonance imaging pre-discharge and at 4 months follow-up were the validation cohort. Remodeling was defined as increase in LV end-diastolic volume between discharge and follow-up (ΔEDV >0). Circulating miRNAs were measured by microarrays and PCR. 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 down-regulated in patients with remodeling (ΔEDV >0) compared to 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 (Nt-pro-BNP) to predict remodeling (area under the receiver operating characteristic curve of 0.74 and 0.60, respectively). miR-150 reclassified 54% (95% confidence interval (CI), 5-102%; P=0.03) of patients misclassified by Nt-pro-BNP and 59% (95% CI, 9-108%; P=0.02) of patients misclassified by a multi-parameter clinical model including age, gender, and admission levels of troponin I, creatine kinase, and Nt-pro-BNP. Conclusions—Low circulating levels of miR-150 are associated with LV remodeling after first STEMI. miR-150 has potential as a novel biomarker in this setting.