Multi-omic and multispecies analysis of right ventricular dysfunction

Jenna B. Mendelson, Jacob D. Sternbach, Michelle J. Doyle, Lauren Mills, Lynn M. Hartweck, Walt Tollison, John P. Carney, Matthew T. Lahti, Richard W. Bianco, Rajat Kalra, Felipe Kazmirczak, Charles Hindmarch, Stephen L. Archer, Kurt W. Prins, Cindy M. Martin

Research output: Contribution to journalArticlepeer-review


Background: Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. Methods: Transcriptomics and proteomics analyses defined the pathways associated with cardiac magnetic resonance imaging (MRI)-derived values of RV hypertrophy, dilation, and dysfunction in control and pulmonary artery banded (PAB) pigs. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare molecular responses across species. Results: PAB pigs displayed significant right ventricle/ventricular (RV) hypertrophy, dilation, and dysfunction as quantified by cardiac magnetic resonance imaging. Transcriptomic and proteomic analyses identified pathways associated with RV dysfunction and remodeling in PAB pigs. Surprisingly, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across the 3 species. FAO and ETC proteins and transcripts were mostly downregulated in rats but were predominately upregulated in PAB pigs, which more closely matched the human response. All species exhibited similar dysregulation of the dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy pathways. Conclusions: The porcine metabolic molecular signature was more similar to human RVF than rodents. These data suggest there may be divergent molecular responses of RVF across species, and pigs may more accurately recapitulate metabolic aspects of human RVF.

Original languageEnglish (US)
Pages (from-to)303-313
Number of pages11
JournalJournal of Heart and Lung Transplantation
Issue number2
StatePublished - Feb 2024

Bibliographical note

Publisher Copyright:
© 2023 International Society for the Heart and Lung Transplantation


  • RV
  • cardiac MRI
  • comparative study
  • proteomics
  • transcriptomics

PubMed: MeSH publication types

  • Journal Article


Dive into the research topics of 'Multi-omic and multispecies analysis of right ventricular dysfunction'. Together they form a unique fingerprint.

Cite this