Abstract 17711: Myocardial Long Non-coding RNA Expression Exhibits Chamber- and Disease-Specific Signatures in Human Right Ventricle
Background: Eukaryotic genome transcription is pervasive; >90% of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs). It is known that human cardiac lncRNA expression is dynamically regulated in the left ventricle (LV) with heart failure (HF). However, it remains unclear how lncRNA expression is regulated in normal and failing right ventricle (RV).
Methods & Results: Paired-end RNA sequencing (RNASeq) was conducted using RNA isolated from paired RV and LV samples from non-failing (NF) hearts (n=5), as well as from the RVs of dilated non-ischemic (DCM, n=11) and ischemic (ICM, n=11) human failing hearts. A total of 970568044 read pairs were obtained. RNASeq analysis revealed high abundance of lncRNAs of mitochondrial origin in both RV (58.8%) and LV (56.5%). Among the 4129 lncRNAs significantly expressed (≥1 reads per killobase exon per million mapped reads) in human myocardium, 439 (10.6%) were differentially expressed (absolute fold-change≧1.2, adjusted P<0.05) between non-failing RV and LV. Hierarchical clustering analyses showed that the expression profiles of lncRNAs, but not mRNAs, distinguished NF RV from NF LV (Figure). There were 667 (459 up,208 down) and 690 (513 up,177 down) lncRNAs dysregulated in the RVs with ICM and DCM, respectively, compared with NF RV samples. Principal component analyses showed that the expression signature of RV lncRNAs, but not mRNAs, discriminates both non-failing from failing RVs and the etiology of heart failure (ICM vs DCM) (Figure).
Conclusion: Human cardiac lncRNA expression exhibits chamber-specific signatures and discriminates RV from LV. RV lncRNAs are dynamically regulated with advanced HF, and the expression profiles of RV lncRNAs discriminate failing hearts of different etiologies. Taken together, these results suggest that lncRNAs may play an important role in shaping chamber-specific ventricular function and may contribute to etiology-specific RV remodeling processes during HF.
Author Disclosures: K. Yang: None. T.G. Di Salvo: None.
- © 2014 by American Heart Association, Inc.