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Related Experiment Video

Updated: Jul 15, 2025

Assessment of Right Ventricular Structure and Function in Mouse Model of Pulmonary Artery Constriction by Transthoracic Echocardiography
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Multi-omic and multispecies analysis of right ventricular dysfunction.

Jenna B Mendelson1, Jacob D Sternbach2, Michelle J Doyle2

  • 1Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota.

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
|October 2, 2023
PubMed
Summary
This summary is machine-generated.

Right ventricular failure (RVF) treatments are lacking due to undefined targets. Pigs, unlike rats, show molecular changes in fatty acid oxidation and electron transport chain proteins that mirror human RVF responses.

Keywords:
RVcardiac MRIcomparative studyproteomicstranscriptomics

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Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Comparative Pathology

Background:

  • Right ventricular failure (RVF) is a significant cause of death in cardiovascular diseases, yet lacks effective treatments due to poorly defined therapeutic targets.
  • Current molecular studies on RVF primarily use small animal models, with limited data from large animal models and cross-species comparisons.
  • Understanding the molecular differences in RVF across species is crucial for developing effective human therapies.

Purpose of the Study:

  • To compare the molecular mediators of right ventricular failure (RVF) across different species.
  • To evaluate the utility of a large animal model (pigs) in recapitulating human RVF molecular signatures.
  • To identify potential therapeutic targets for RVF by comparing transcriptomic and proteomic data.

Main Methods:

  • Transcriptomic and proteomic analyses were performed on control and pulmonary artery banded (PAB) pigs to assess RV hypertrophy, dilation, and dysfunction.
  • Publicly available transcriptomic/proteomic data from rat models of RVF and human patients with pulmonary arterial hypertension were analyzed.
  • Molecular responses were compared across pigs, rats, and humans to identify conserved and divergent pathways.

Main Results:

  • Pulmonary artery banding in pigs induced significant RV hypertrophy, dilation, and dysfunction, confirmed by cardiac MRI.
  • Transcriptomic and proteomic analyses revealed distinct patterns of fatty acid oxidation (FAO) and electron transport chain (ETC) protein regulation between rats and pigs.
  • While rats showed downregulation of FAO and ETC, pigs exhibited upregulation, aligning more closely with human RVF molecular profiles. Both species showed dysregulation in dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy pathways.

Conclusions:

  • The metabolic molecular profile of RVF in pigs more closely resembles that of humans compared to rodents.
  • These findings suggest species-specific differences in the molecular mechanisms underlying RVF.
  • Pigs represent a more relevant large animal model for studying the metabolic aspects of human RVF, potentially aiding in the identification of therapeutic targets.