Proteomics Dissection of Cardiac Protein Profiles of Humans and Model Organisms

Abstract

The study of human cardiac pathologies often relies on research conducted in model organisms to gain molecular insight into disease and to develop novel treatment strategies; however, translating findings from model organisms back to human can present a significant challenge, in part due to a lack of knowledge about the differences across species in cardiac protein abundances and their interactions. Here we set out to bridge this knowledge gap by presenting a global analysis of cardiac protein expression profiles in humans and commonly used model organisms. Using quantitative mass spectrometry-based proteomics, we measured the abundance of ~7,000 proteins in samples from the separate chambers of human, pig, horse, rat, mouse and zebrafish hearts. This knowledgebase of cardiac protein signatures is accessible through an online database at: atlas.cardiacproteomics.com. Quantitative comparison of the protein profiles support the pig as model organism of choice for arrhythmogenic right ventricular cardiomyopathy whereas comparison of profiles from the two-chambered zebrafish heart suggests a better resemblance to the right side of mammalian hearts. This proteomics resource

Large Animal Models in Cardiovascular Research

“…It is useful in qualitative and quantitative analyses of disease biomarkers in various specimens that lead to not only diagnosis but also risk stratification and guidance in the selection of therapeutic modalities [64]. Linscheid et al recently performed systematic analyses of cardiac proteomes across cardiac chambers in humans, pigs, and four commonly used animal models and identified and quantified approximately 7,000 proteins, comparing them with respect to cardiac function and mechanisms of diseases [65]. Tamiyakul et al performed a proteome analysis on the myocardium of the DMD pig model that showed an altered abundance of several proteins such as reduction of myosin-6, which is directly involved in muscle contraction [66] and validated the results by complementary mass spectrometry [67].…”