Objectives: We aim to explore the Epicardial Adipose Tissue (EAT) proteome to identify its role in the genesis of postoperative atrial fibrillation (AF). Methods: EAT samples were collected in 76 patients with no history of AF undergoing CABG. 50 were incubated in culture medium. Conditioned media representing EAT secretome were harvested and proteins extracted from the remaining tissues. Samples were analysed by two-dimensional difference in-gel electrophoresis (2D-DIGE) and high-performance liquid chromatographytandem mass spectrometry (HPLC-MSIMS). Gene expression analysis was performed on 24 samples (8 AF vs. 16 controls). Findings were validated by Western blotting. Results: 20 secretome samples (10 vs. 10) and 12 EAT extracts (6 vs. 6), divided according to development of postoperative AF, were analysed by proteomics. The proteomics analysis returned 35 differentially expressed protein spots in the secretome and 16 differentially expressed protein spots in the EAT extracts (p<O.05, fold change> 1.2). Gelsolin (GSN) was significantly reduced in AF (p=O.03). Dimethylarginine dimethylaminohydrolase 2 (DDAH2) was upregulated in AF (p=O.04). SBP1 was increased in AF for the secretome and reduced in the EAT extracts. Catalase (CATA) was downregulated in AF. GSN was consistently found to be downregulated in the AF group by three independent techniques. Conclusions. Systemic inflammatory response to cardiac surgery and oxidative stress are known triggers for AF. GSN exerts antinflammatory properties by severing actin filaments. DDAH2 degrades nitric oxide synthase inhibitor ADMA (asymmetric dimethylarginine), known to increase oxidative stress.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:677184 |
| Date | January 2015 |
| Creators | Viviano, Alessandro |
| Publisher | St George's, University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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