Right ventricular myocardial biomarkers in human heart failure.
BACKGROUND
Right ventricular (RV) dysfunction contributes to mortality in chronic heart failure (HF). However, the molecular mechanisms of RV failure remain poorly understood, and RV myocardial biomarkers have yet to be developed.


RESULTS
We performed RNA sequencing (RNA-seq) on 22 explanted human HF RVs and 5 unused donor human heart RVs (DON RV) and compared results to those recently reported from 16 explanted human LVs We used Bowtie-Tophat for transcript alignment and transcriptome assembly, DESeq for identification of differentially expressed genes (DEGs) and Ingenuity for exploration of gene ontologies. In the HF RV, RNA-seq identified 130,790 total RNA transcripts including 13,272 protein coding genes, 10,831 long non-coding RNA genes and 8,605 pseudogenes. There were 800-1000 DEGs between DON and HF RV comparison groups with differences concentrated in cytoskeletal, basement membrane, extracellular matrix (ECM), inflammatory mediator, hemostasis, membrane transport and transcription factor genes, lncRNAs and pseudogenes. In an unbiased approach, the top 10 DEGs SERPINA3, SERPINA5, LCN6, LCN10, STEAP4, AKR1C1, STAC2, SPARCL1, VSIG4 and F8 exhibited no overlap in read counts between DON and HF RVs, high sensitivities, specificities, predictive values and areas under the receiver operating characteristic curves. STEAP4, SPARCL1 and VSIG4 were differentially expressed between RVs and LVs, supporting their roles as RV-specific myocardial biomarkers.


CONCLUSIONS
Unbiased, comprehensive profiling of the RV transcriptome by RNA-seq suggests structural changes and abnormalities in inflammatory processes and yields specific, novel HF RV vs HF LV myocardial biomarkers not previously identified by more limited transcriptome profiling approaches.
Division of Cardiovascular Medicine, Vanderbilt Heart and Vascular Institute, Nashville, Tennessee. Electronic address: thomas.g.disalvo@vanderbilt.edu.
Thomas G
TG
di Salvo
Department of Pharmacology, National Taiwan University, Taipei, Taiwan.
Kai-Chien
KC
Yang
Division of Cardiovascular Medicine, Vanderbilt Heart and Vascular Institute, Nashville, Tennessee.
Evan
E
Brittain
Division of Cardiovascular Surgery, Vanderbilt Heart and Vascular Institute, Nashville, Tennessee.
Tarek
T
Absi
Division of Cardiovascular Surgery, Vanderbilt Heart and Vascular Institute, Nashville, Tennessee.
Simon
S
Maltais
Pulmonary and Critical Care Medicine, Vanderbilt Department of Medicine, Nashville, Tennessee.
Anna
A
Hemnes
D000328:Adult; D015415:Biomarkers; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers / Q000235:genetics; D006333:Heart Failure / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000235:genetics; D014019:Tissue Donors; D018497:Ventricular Dysfunction, Right / Q000175:diagnosis* / Q000235:genetics*
D015415:Biomarkers; D005819:Genetic Markers; D012313:RNA
Human heart failure; RNA-seq; biomarkers; myocardial; right ventricle; transcriptome