One particular focus of the Group's work centres on the chemical hypochlorite, which is a powerful oxidising agent. Most people will be familiar with the anti-bacterial action of this chemical, as it is the major active component of household bleach. Interestingly, hypochlorite is also made by white blood cells in our body, in a reaction that involves the enzyme myeloperoxidase, to kill invading bacteria and other pathogens, and plays a key role in the immune defence system. Usually the generation of this highly dangerous compound is closely controlled, but it is now known that if this process becomes uncontrolled as occurs in some diseases damage can occur to the body's own cells and structures. In recent years it has become clear that myeloperoxidase is present and active within the artery wall and may contribute to the development of atherosclerotic lesions and heart disease plaques. In particular it has been shown that people with a high concentration of myeloperoxidase in their blood have a higher risk of developing heart disease. How this enzyme generates damage to the artery wall, and more importantly, how this might be prevented is a key goal of some of the groups current research.
The Group is also striving to understand how chemical reactions associated with diabetes and the inflammatory condition systemic lupus, impact on the development of heart disease. Both of these conditions pre-dispose patients to the development of atherosclerosis and an increased risk of dying from heart disease, though the processes by which this occurs are not fully understood. In the case of diabetes, the group have been studying how the high (and poorly-controlled) sugar concentrations present in the blood of people with diabetes affects the uptake and metabolism of cholesterol into the artery wall. It has been shown that modification of proteins by glucose can occur rapidly to give modified structures, which are internalised by cells. In the case of the particles that transport cholesterol in the blood (low-density lipoproteins) this enhanced rate of cellular uptake results in the accumulation of cholesterol and fats in the artery wall. This accumulation is known to be associated with the development of atherosclerotic lesions. In recent work the group has been examining what sorts of compounds might prevent these protein changes, and a number of lead compounds have been identified which can block cholesterol accumulation into cells.
Another facet of the work carried out by this group is on the role of metal ions in the development of damage to the artery wall. It has long been postulated that certain metal ions, such as iron and copper, might play a role in the development of heart disease, and large population studies have shown that this can indeed be the case. However direct experimental evidence for the presence of metal ions in the artery wall, and their role in disease development is unclear. The group have been developing techniques that allow these questions to be addressed. We have been able to show that there are indeed elevated levels of iron and copper in advanced human atherosclerotic lesions and that the level of these materials correlates with some of the markers of disease. Current work is focused on how these metal ions cause damage, and whether it is possible to prevent the progression of heart disease by deactivating, or removing, these metal ions.
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