Abstract 15090: Circulating miR-503 and miR-374b-5p are associated With Heart Failure

Introduction: Circulating microRNA (miRNAs) profiles are dysregulated in heart failure (HF) suggesting possible diagnostic and prognostic applications. In addition, miRNAs may yield insights into the pathophysiology of HF and provide targets for therapeutic intervention. We sought to identify miRNAs diagnostic utility in HF and to further investigate selected miRNAs as potential targets for therapeutic intervention. Hypothesis: We hypothesized that distinct circulating miRNAs are dysregulated in HF and may be potentially important targets of therapy to improve outcomes for HF. Methods: Plasma miRNAs levels were profiled from 338 well-characterized HF patients and 208 age-matched controls without HF. We also examined selected miRNAs expression in a rat post-myocardial infarction (MI) model. Target predictive databases were used to identify potential miRNA targets. Results: Comparison between HF and non-HF controls was carried out by multivariate analysis. Seventy five miRNAs differed significantly between HF and non-HF controls after adjustment for age, hypertension, diabetes and atrial fibrillation (p-value after FDR<0.01). Twenty four miRNAs with AUC>0.65 , p<0.001 (for discrimination of HF from non-HF controls on receiver-operator analysis) were highly up- or down-regulated significantly in clinical data comparing HF vs non-HF controls and were further examined in plasma samples from a rat post-MI model. Results showed that levels of miR-503 (AUC=0.73, FC (Fold Change) =1.69, p<0.001) was higher and of miR-374b-5p (AUC=0.71, FC=-1.45, p<0.001) lower when comparing HF patients with non-HF controls. In rat experimental model, levels of miR-503 (FC=2.21, p=0.017) increased and of miR-374b-5p (FC=-1.35, p=0.02) decreased after post-MI at Day 2 and Day 7, but not significant in Day 14 comparing with sham. MiR-503 has been reported to target CCNE1 and cdc25A. The predicted target for miR-374b is NPPB . The roles of miR-503 and miR-374b-5p in HF warrant further investigation using both in-vitro and in-vivo preclinical HF models. Conclusion: We provide a detailed study of circulating miRNA profiling in both clinical HF and experimental model. We demonstrated that circulating miR-503 and miR-374b-5p are associated with HF.