A Proof of Principle 2D Spatial Proteome Mapping Analysis Reveals Distinct Regional Differences in the Cardiac Proteome
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 int...
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| Main Authors: | , , , , , , , , , , , |
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MDPI AG
2024-08-01
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| Online Access: | https://www.mdpi.com/2075-1729/14/8/970 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Wendy E. Heywood |
| collection | DOAJ |
| container_title | Life |
| description | 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. |
| format | Article |
| id | doaj-art-c8a6dfe6be694246b433b3a2ecda8baf |
| institution | Directory of Open Access Journals |
| issn | 2075-1729 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| spelling | doaj-art-c8a6dfe6be694246b433b3a2ecda8baf2025-08-19T22:59:26ZengMDPI AGLife2075-17292024-08-0114897010.3390/life14080970A Proof of Principle 2D Spatial Proteome Mapping Analysis Reveals Distinct Regional Differences in the Cardiac ProteomeWendy E. Heywood0Jon Searle1Richard Collis2Ivan Doykov3Michael Ashworth4Neil Sebire5Andrew Bamber6Mathias Gautel7Simon Eaton8Caroline J. Coats9Perry M. Elliott10Kevin Mills11UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UKUCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UKInstitute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UKUCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UKHistopathology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 1EH, UKHistopathology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 1EH, UKHistopathology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 1EH, UKRandall Division of Cell and Molecular Biophysics, Muscle Signalling Section, King’s College, London WC2E 2LS, UKUCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UKInstitute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UKInstitute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UKUCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UKProteomics 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.https://www.mdpi.com/2075-1729/14/8/970heartproteomemitochondriadesmoglein-2proteomics |
| spellingShingle | 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 A Proof of Principle 2D Spatial Proteome Mapping Analysis Reveals Distinct Regional Differences in the Cardiac Proteome heart proteome mitochondria desmoglein-2 proteomics |
| title | A Proof of Principle 2D Spatial Proteome Mapping Analysis Reveals Distinct Regional Differences in the Cardiac Proteome |
| title_full | A Proof of Principle 2D Spatial Proteome Mapping Analysis Reveals Distinct Regional Differences in the Cardiac Proteome |
| title_fullStr | A Proof of Principle 2D Spatial Proteome Mapping Analysis Reveals Distinct Regional Differences in the Cardiac Proteome |
| title_full_unstemmed | A Proof of Principle 2D Spatial Proteome Mapping Analysis Reveals Distinct Regional Differences in the Cardiac Proteome |
| title_short | A Proof of Principle 2D Spatial Proteome Mapping Analysis Reveals Distinct Regional Differences in the Cardiac Proteome |
| title_sort | proof of principle 2d spatial proteome mapping analysis reveals distinct regional differences in the cardiac proteome |
| topic | heart proteome mitochondria desmoglein-2 proteomics |
| url | https://www.mdpi.com/2075-1729/14/8/970 |
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