Influence of Diet in Heart Failure: Role of Short Chain Fatty Acids in monocyte phenotype (360G-Wellcome-207003_Z_17_Z)
The aim of this project is to find out if small chain fatty acids (SCFA's) play a role in heart failure via their interaction with inflammatory cells and the regulation of inflammatory cytokine production that can lead to fibrosis and diastolic dysfunction. SCFA's are produced by the gut microbiota following the fermentation of soluble fibres that are contained in the diet. There is evidence of dramatic changes in gut microbiota populations in patients with heart failure and a clear link between heart failure and the amount of fibre in the diet. The presence of free fatty acid receptors (FFAR) on monocytes might link SCFA with the release of inflammatory cytokines possibly leading to progressive damage of the cardiovascular system. FFARs are expressed on monocytes and macrophages. This project will firstly quantify FFAR3 expression in a cohort of 44 patient-derived monocyte cDNA samples. FFAR3 expression will be correlated with previously aquired data on FFAR2 and inflammatory gene expression and serum cytokine data. Monocytes and macrophages are known to be the major drivers of inflammatory and fibrotic processes in heart failure. This project will investigate the role of SCFA's in regulating human macrophage differentiation in response to known drviers of M1/M2 phenotype.
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