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The role of Glutathione Peroxidase 4 (GPX4) and the GPX4 single-nucleotide polymorphism (SNP), rs713041, in metabolic syndrome associated vascular dysfunction

People Involved

Project Description

High blood sugar, high blood pressure, and obesity are all features of the ‘umbrella term’ metabolic syndrome (MetS) which affects 1 in 3 people over 50 years old in the UK. MetS increases the risk of developing heart disease and in particular the conditions atherosclerosis (build-up of fatty plaques in the blood vessels), heart failure, and stroke.

MetS impacts the cardiovascular system (i.e. the heart and blood vessels) in a range of diverse ways, but chronic inflammation, oxidative stress, and elevated blood glucose levels are the main effects. Understanding how these factors damage blood vessel cells and discovering biomarkers of early damage can help avoid cardiovascular illnesses and effectively control risk factors. Cells called vascular smooth muscle cells (VSMCs) form an important part of the blood vessel and help to control both blood flow and blood pressure. In atherosclerosis caused by MetS, these cells increase in number (i.e. proliferate), move from the healthy blood vessels to the fatty plaque (i.e. migration), where they absorb fat (i.e. become foam cells) and die prematurely (a process called ferroptosis), which combined increases the risk of the fatty plaque rupturing and causing a blockage in the blood vessel. This project will therefore try to identify components within these cells that may cause their malfunctioning, and one possible component is glutathione peroxidase 4 (GPX4).

GPX4, a selenium-containing protein, protects cells, especially VSMCs, from oxidative stress and early cell death (ferroptosis). However, GPX4 does not work properly in the setting of MetS and a mutation in the GPX4 gene (called a SNP) has been linked to an increased risk of MetS features like atherosclerosis. We will use cells (i.e. VSMCs) that we have previously grown from the blood vessels of mice that have the GPX4 SNP/mutation and normal mice to investigate how the GPX4 mutation and selenium status affect biological pathways that lead to ferroptosis, inflammation, and oxidative stress to identify markers of atherosclerosis.

Type of Project Research Grant
Status Project Live
Funder(s) Tenovus Scotland
Value £14,750.00
Project Dates Sep 1, 2023 - Apr 30, 2025

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