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A Proof of Principle 2D Spatial Proteome Mapping Analysis Reveals Distinct Regional Differences in the Cardiac Proteome

Authors :
Wendy E. Heywood
Jon Searle
Richard Collis
Ivan Doykov
Michael Ashworth
Neil Sebire
Andrew Bamber
Mathias Gautel
Simon Eaton
Caroline J. Coats
Perry M. Elliott
Kevin Mills
Source :
Life, Vol 14, Iss 8, p 970 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Proteomics studies often explore phenotypic differences between whole organs and systems. Within the heart, more subtle variation exists. To date, differences in the underlying proteome are only described between whole cardiac chambers. This study, using the bovine heart as a model, investigates inter-regional differences and assesses the feasibility of measuring detailed, cross-tissue variance in the cardiac proteome. Using a bovine heart, we created a two-dimensional section through a plane going through two chambers. This plane was further sectioned into 4 × 4 mm cubes and analysed using label-free proteomics. We identified three distinct proteomes. When mapped to the extracted sections, the proteomes corresponded largely to the outer wall of the right ventricle and secondly to the outer wall of the left ventricle, right atrial appendage, tricuspid and mitral valves, modulator band, and parts of the left atrium. The third separate proteome corresponded to the inner walls of the left and right ventricles, septum, and left atrial appendage. Differential protein abundancies indicated differences in energy metabolism between regions. Data analyses of the mitochondrial proteins revealed a variable pattern of abundances of complexes I–V between the proteomes, indicating differences in the bioenergetics of the different cardiac sub-proteomes. Mapping of disease-associated proteins interestingly showed desmoglein-2, for which defects in this protein are known to cause Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, which was present predominantly in the outer wall of the left ventricle. This study highlights that organs can have variable proteomes that do not necessarily correspond to anatomical features.

Details

Language :
English
ISSN :
20751729
Volume :
14
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Life
Publication Type :
Academic Journal
Accession number :
edsdoj.8a6dfe6be694246b433b3a2ecda8baf
Document Type :
article
Full Text :
https://doi.org/10.3390/life14080970