Changes in transcriptomic landscape in human end-stage heart failure with distinct etiology

Heart failure (HF) is the ultimate outcome of a variety of heart diseases, including restrictive cardiomyopathy (RCM), ischemic heart disease (IHD), and valvular heart disease (VHD). To date, accumulating evidence has suggested an important role of noncoding RNAs (ncRNAs) in HF. We performed RNA-sequencing studies with myocardial mRNAs/lncRNAs/circRNAs/miRNAs from non-failing hearts (donor heart tissue from heart transplantation) and three groups of patients with HF (RCM, IHD, and VHD). HF-related gene regulatory networks and gene co-expression networks were constructed based on the interaction relationship and expression profiles of differentially expressed mRNAs/ncRNAs. Our results indicated that HF with different etiologies is regulated by complex lncRNA/circRNA/miRNA/mRNA regulatory networks, comprising common pathways that are shared by all HF types as well as distinct pathways that are enriched in specific HF types. In addition, the HF biomarkers identified in our study have an important clinical application value in HF staging and HF type diagnosis.