Right ventricular myocardial biomarkers in human heart failure

Thomas G. Di Salvo, Kai Chien Yang, Evan Brittain, Tarek Absi, Simon Maltais, Anna Hemnes

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)398-411
Number of pages14
JournalJournal of Cardiac Failure
Volume21
Issue number5
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Heart Failure
Biomarkers
RNA Sequence Analysis
Long Noncoding RNA
Pseudogenes
Genes
Transcriptome
Right Ventricular Dysfunction
Gene Ontology
Gene Expression Profiling
Hemostasis
Basement Membrane
ROC Curve
Extracellular Matrix
Transcription Factors
RNA
Sensitivity and Specificity
Membranes
Mortality
Proteins

Keywords

  • biomarkers
  • Human heart failure
  • right ventricle
  • RNA-seq
  • transcriptome myocardial

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Right ventricular myocardial biomarkers in human heart failure. / Di Salvo, Thomas G.; Yang, Kai Chien; Brittain, Evan; Absi, Tarek; Maltais, Simon; Hemnes, Anna.

In: Journal of Cardiac Failure, Vol. 21, No. 5, 01.01.2015, p. 398-411.

Research output: Contribution to journalArticle

Di Salvo, TG, Yang, KC, Brittain, E, Absi, T, Maltais, S & Hemnes, A 2015, 'Right ventricular myocardial biomarkers in human heart failure', Journal of Cardiac Failure, vol. 21, no. 5, pp. 398-411. https://doi.org/10.1016/j.cardfail.2015.02.005
Di Salvo, Thomas G. ; Yang, Kai Chien ; Brittain, Evan ; Absi, Tarek ; Maltais, Simon ; Hemnes, Anna. / Right ventricular myocardial biomarkers in human heart failure. In: Journal of Cardiac Failure. 2015 ; Vol. 21, No. 5. pp. 398-411.
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AB - 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. Methods and 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.

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