Saudi Cultural Missions Theses & Dissertations

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The Anti-inflammatory Effects of Metformin on Human Pro-inflammatory Macrophages
(2023-06-23) Alqurashi, Noor; Rena, Graham
Macrophages are a type of immune cells that have a key role in atherosclerotic plaque development and as such possible target for cardiovascular disease (CVD) therapy. In mouse and human lesions, macrophages adhering to both M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes are present, with M1 being the most common phenotype. The type 2 diabetes drug metformin is thought to reduce inflammation by reducing the polarisation process to M1 macrophages, with AMPK activation likely to be an important mediator of this effect. In this thesis, I have used state-of-the-art data-independent acquisition (DIA) proteomics to perform a systems-wide comparison of the effect of metformin and a selective AMPK agonist A769662 on the polarisation and differentiation processes in THP-1 cells, a human macrophage cell line. This work highlighted the modulation of proteins linked to inflammation, cell adhesion, migration,
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