Abstract 12952: Deep Sequencing Reveals Distinct Right Ventricular miRNA Signature in Failing Human Heart
Introduction: Right ventricular (RV) dysfunction contributes critically to the pathophysiology of congestive heart failure (HF). Impaired RV function independently predicts the mortality in patients with advanced HF. It has been well-documented that miRNA dysregulation in left ventricle (LV) plays an important role in pathogenesis of HF; however, it remains unclear how miRNAs are regulated in RV during HF.
Methods and Results: Deep sequencing of small RNAs was conducted using RNA isolated from paired RV and LV samples from non-failing (NF) hearts (n=5), as well as from the RV of dilated non-ischemic (DCM, n=11) and ischemic (ICM, n=11) human failing hearts. A total of 624697446 sequencing reads were obtained and 492 miRNAs were detected in the human cardiac samples. Twenty-four miRNAs are differentially expressed in non-failing LV and RV samples (absolute fold-change≧1.2, adjusted P<0.05), including cardiac-enriched miRNAs miR-1 (1.36-fold higher in RV, P=0.03) and miR-208b (1.55-fold lower in RV, P=0.04). A total of 88 (68 up/20 down) and 121 (102 up/15 down) RV miRNAs are differentially expressed in ICM and DCM, respectively, compared with non-failing RV samples. Only ~25% (24 out of 88 in ICM, 32 out of 121 in DCM) of the differentially expressed miRNAs in failing RV show congruent changes in failing LV. Among the miRNAs that change specifically in failing RV, 43 are regulated concordantly in ICM and DCM. Three of the RV-enriched miRNAs, miR-493, miR-125b and miR-204, are upregulated with HF in RV but unchanged in LV. In addition, miR-490 showed discordant regulation between failing LV and RV, where miR-490 is downregulated in LV but upregulated in RV, with either ICM or DCM. These data suggest that miRNAs are regulated differently in LV and RV in failing hearts, which may contribute to the distinct RV remodeling process during HF.
Conclusions: Although less than 5% of the myocardial miRNAs express differentially in RV and LV at baseline, myocardial miRNome responds to HF with marked differences between ventricular chambers. The distinct miRNA expression signature may contribute to the unique RV remodeling process with HF. Targeting RV-specific miRNA dysregulation may provide a novel therapeutic approach against RV dysfunction during HF.
Author Disclosures: K. Yang: None. T.G. Di Salvo: None.
- © 2014 by American Heart Association, Inc.