Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes
| Autor: | Harriet McKinney, Leong L. Ng, Maik Pietzner, Simona D'Amore, Julian L. Griffin, Bekir Erguener, Michael Allison, John J Lambourne, Mattia Frontini, Matthew C Sims, Paul D. W. Kirk, Adrian Park, Denis Seyres, Kate Downes, Carly Kempster, Claudia Langenberg, Luigi Grassi, Luca Stefanucci, Frances Burden, Paulenne Quinn, Claire Adams, Albert Koulman, Karola Rehnström, Gabriele Mocciaro, Christoph Bock, Thong Huy Cao, Amy Frary, Samantha Farrow, Roman Kreuzhuber, Michele Vacca, David B. Savage, Oliver Slingsby, Alessandra Cabassi, Joana Batista |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
education.field_of_study business.industry Population Bioinformatics medicine.disease Phenotype Pathophysiology 3. Good health Pathogenesis Transcriptome 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis Medicine Epigenetics Lipodystrophy business education 030304 developmental biology Epigenomics |
| Popis: | Improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis are ongoing healthcare challenges. Using plasma biomarkers analysis coupled with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (obese and lipodystrophy) and comparing these to lean individuals and blood donors, the present study identifies the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells and shows 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, six months after bariatric surgery shows the loss of the patterns of abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individuals, this occurs via the establishment of novel gene expression landscapes. Netosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention. Taken together, by integrating across data layers, the observed molecular and metabolic differences form a disease signature that is able to discriminate, amongst the blood donors, those individuals with a higher likelihood of having cardiometabolic syndrome, even when not presenting with the classic features. |
| Databáze: | OpenAIRE |
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