Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes.
Authors
Cabassi, Alessandra
Lambourne, John J
Burden, Frances
Farrow, Samantha
McKinney, Harriet
Batista, Joana
Kempster, Carly
Pietzner, Maik
Slingsby, Oliver
Cao, Thong Huy
Quinn, Paulene A
Stefanucci, Luca
Sims, Matthew C
Rehnstrom, Karola
Adams, Claire L
Frary, Amy
Ergüener, Bekir
Kreuzhuber, Roman
Mocciaro, Gabriele
D'Amore, Simona
Grassi, Luigi
Griffin, Julian L
Ng, Leong Loke
Park, Adrian
Savage, David B
Bock, Christoph
Downes, Kate
Allison, Michael
Vacca, Michele
Frontini, Mattia
Publication Date
2022-03-12Journal Title
Clin Epigenetics
ISSN
1868-7075
Publisher
Springer Science and Business Media LLC
Volume
14
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Seyres, D., Cabassi, A., Lambourne, J. J., Burden, F., Farrow, S., McKinney, H., Batista, J., et al. (2022). Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes.. Clin Epigenetics, 14 (1) https://doi.org/10.1186/s13148-022-01257-z
Description
Funder: British Heart Foundation Cambridge Centre of Excellence
Funder: The National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and NIHR Rare Disease Translational Research Collaboration
Funder: NHS Health Education England
Funder: NIHR Cambridge Biomedical Research Centre
Funder: Isaac Newton fellowship
Funder: NIHR Leicester Biomedical Research Centre and the John and Lucille Van Geest Foundation
Abstract
BACKGROUND: This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature. METHODS/RESULTS: We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers. The characterisation of the same obese group, 6 months after bariatric surgery, revealed the loss of the abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individuals, this occurred via the establishment of novel gene expression landscapes. NETosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention. CONCLUSIONS: We showed that the morbidly obese and lipodystrophy groups, despite some differences, shared a common cardiometabolic syndrome signature. We also showed that this could be used to discriminate, amongst the normal population, those individuals with a higher likelihood of presenting with the disease, even when not displaying the classic features.
Keywords
Research, Cardiovascular epigenetics, Epigenetics, Metabolites, Lipids, Multi-omics, Obesity, Lipodystrophy, Bariatric surgery, Classification, Innate immune cells, Cardiometabolic syndrome
Sponsorship
Medical Research Council (MC_UU_12012/1)
Wellcome Trust (107064/Z/15/Z)
Medical Research Council (MR/R002363/1)
Identifiers
s13148-022-01257-z, 1257
External DOI: https://doi.org/10.1186/s13148-022-01257-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334922
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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