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The role of the ERK1: STAT1 serine 727 phosphorylation axis on key atherosclerosis associated cellular processes and the anti-atherogenic actions of hydroxytyrosol

Al-Ahmadi, Wajdan 2019. The role of the ERK1: STAT1 serine 727 phosphorylation axis on key atherosclerosis associated cellular processes and the anti-atherogenic actions of hydroxytyrosol. PhD Thesis, Cardiff University.
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Abstract

Atherosclerosis, a chronic inflammatory disease of the vasculature charactarised by the build-up of fatty deposits within the walls of arteries is the underlying cause of cardiovascular diseases (CVD) such as myocardial infarction and stroke. It is responsible for most deaths in westernised societies with numbers increasing at a marked rate in developing countries. A range of immune cells, such as macrophages play a pivotal role in the pathogenesis of atherosclerosis through the action of various cytokines, such as interferon-γ (IFN-γ) that orchestrates the inflammatory response via key signalling pathways, such as extracellular-signal regulated kinases (ERKs), and transcription factors such as signal transducer and activator of transcription-1 (STAT1) that is activated by changes in phosphorylation at specific residues. In this study the availability of ERK1 (ERK1-/-) mice and STAT1 knock-in mice (STAT1S727A) in which the serine 727 phosphorylation site, a target for ERKs action, had been mutated to alanine provided an excellent opportunity to probe the role of the ERK1:STAT1 serine 727 phosphorylation axis on key atherosclerosis-associated processes and atherosclerosis-associated gene expression in vitro. Current therapies against atherosclerosis are not fully effective; this has generated substantial interest on nutraceuticals, such as hydroxytyrosol (HT) found in olives. This study aimed to investigate the role of the ERK1:STAT1 serine 727 phosphorylation axis on key atherosclerosis-associated processes in BMDM regulated by HT in vitro and probe the effects of HT in vivo in wild type C57BL/6J mice fed a high fat diet (HFD) for 3 weeks and in male and female LDL receptor deficient mice (LDLR-/-) fed a HFD for 12 weeks. The findings of these studies showed an important role for ERK1 and STAT1 serine 727 phosphorylation on the expression of a large number of atherosclerosis-associated genes and some key cellular processes. In addition, to the HT anti-atherogenic and potential athero-protective effects in vivo.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Biosciences
Funders: Saudi scholarship
Date of First Compliant Deposit: 8 July 2019
Last Modified: 08 Jul 2020 02:05
URI: http://orca.cf.ac.uk/id/eprint/123990

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