Repository logo
 

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes.

Published version
Peer-reviewed

Change log

Authors

Cabassi, Alessandra 
Lambourne, John J 
Burden, Frances 
Farrow, Samantha 

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.

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

Keywords

Research, Cardiovascular epigenetics, Epigenetics, Metabolites, Lipids, Multi-omics, Obesity, Lipodystrophy, Bariatric surgery, Classification, Innate immune cells, Cardiometabolic syndrome

Journal Title

Clin Epigenetics

Conference Name

Journal ISSN

1868-7075
1868-7083

Volume Title

14

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12012/1)
Wellcome Trust (107064/Z/15/Z)
Medical Research Council (MR/R002363/1)