Quantitative proteome comparison of human hearts with those of model organisms

PLoS Biol. 2021 Apr 19;19(4):e3001144. doi: 10.1371/journal.pbio.3001144. eCollection 2021 Apr.

Abstract

Delineating human cardiac pathologies and their basic molecular mechanisms relies on research conducted in model organisms. Yet translating findings from preclinical models to humans present a significant challenge, in part due to differences in cardiac protein expression between humans and model organisms. Proteins immediately determine cellular function, yet their large-scale investigation in hearts has lagged behind those of genes and transcripts. Here, we set out to bridge this knowledge gap: By analyzing protein profiles in humans and commonly used model organisms across cardiac chambers, we determine their commonalities and regional differences. We analyzed cardiac tissue from each chamber of human, pig, horse, rat, mouse, and zebrafish in biological replicates. Using mass spectrometry-based proteomics workflows, we measured and evaluated the abundance of approximately 7,000 proteins in each species. The resulting knowledgebase of cardiac protein signatures is accessible through an online database: atlas.cardiacproteomics.com. Our combined analysis allows for quantitative evaluation of protein abundances across cardiac chambers, as well as comparisons of cardiac protein profiles across model organisms. Up to a quarter of proteins with differential abundances between atria and ventricles showed opposite chamber-specific enrichment between species; these included numerous proteins implicated in cardiac disease. The generated proteomics resource facilitates translational prospects of cardiac studies from model organisms to humans by comparisons of disease-linked protein networks across species.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Heart / physiology
  • Heart Ventricles / chemistry
  • Heart Ventricles / metabolism
  • Horses
  • Humans
  • Mice
  • Models, Animal
  • Myocardium / chemistry
  • Myocardium / metabolism*
  • Organ Specificity
  • Protein Processing, Post-Translational
  • Proteome / analysis
  • Proteome / metabolism*
  • Proteomics / methods
  • Rats
  • Species Specificity
  • Swine
  • Zebrafish

Substances

  • Proteome

Grant support

This work was supported by grants from the Carlsberg Foundation (CF17-0209, https://www.carlsbergfondet.dk/), The Danish Council for independent Research (DFF-4092-00045, https://dff.dk/), and The Novo Nordisk Foundation (NNF15OC0017586. https://novonordiskfonden.dk/) to AL. The Novo Nordisk Foundation Center for Protein Research is funded in part by a generous donation from the Novo Nordisk Foundation (NNF14CC0001, https://novonordiskfonden.dk/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.