Abstract 8443: Circulating MicroRNAs Expression in Human Plasma is Dysregulated by Heart Failure

Abstract

Purpose: Circulating microRNAs (miRNAs) have recently been identified and proposed as novel biomarkers of several diseases. Here we examined miRNAs expression profile of heart failure (HF) patients, NYHA class I-IV, in comparison to matched controls. Methods: We analyzed the expression of 365 miRNAs in plasma samples from healthy donors (n= 5) and NYHA class I-IV HF patients (n= 5/group). MiRNAs expression was evaluated using TaqMan microRNA Arrays followed by a validation step. Results were normalized using miR-532-5p as an internal experimentally validated calibrator with low dispersion of expression levels and null association with HF. Validated miRNAs were examined in the plasma of healthy subjects (n=10) and NYHA class I-IV HF patients (n=10-14/ group). RESULTS: Of ∼190 miRNAs expressed in plasma of healthy subjects and HF patients we were able to identify 17 miRNAs dysregulated by HF (14 up- and 3 down-regulated), with 7 showing no expression in control samples (miR-154,-299, -376a, -379, -409-5p, -548a and -654). Expression analysis of 9 of these 17 miRNAs throughout the 4 NYHA classes showed that miR-154, -221, -376a, -409-5p and -379 are strongly overexpressed (20 to 170 folds vs controls) in all HF subjects while miR-124a, -375 and -451 exhibit a significant downregulation in class I (40%), IV (50%) and III and IV (70 and 90%) respectively. In agreement with a prior study, miR- 423-5p exhibited an increase in all HF subjects, statistically significant in NYHA classes II and IV (3 to 4 folds). Interestingly miR-379 showed marked differences between NYHA classes I and II and II and III. Further, 8 miRNAs (miR-1, -21, 146a, -548a, -299-5p, -331-5p, -654-5p and -376c) differentiated controls from NYHA class IV patients (n=14) exhibiting an up-regulation of 6 to 40 folds. Conclusions: A novel miRNA signature consisting of enhanced expression of 14 and decrease of 3 plasma miRNAs was found in HF patients (NYHA classes I to IV). These findings pave the way for the identification of HF dysregulated miRNAs which can be viewed as promising biomarkers of heart failure.