Former research areas
The aim of the Free Radical Group was to understand how free radicals and oxidants can modify the structure and function of the artery wall by focusing on oxidants generated in the artery wall during inflammation.
Understanding the biochemistry of the free radicals and oxidants that cause damage to the artery wall during atherosclerosis provides us with insight into how and why the disease develops and progresses. This detailed knowledge allows us to strategically develop new approaches that we believe should reduce, or even prevent, the amount of arterial damage caused by these oxidants.
The aim of the Immunobiology Group was to uncover ways to stimulate atherosclerotic plaque regression and increase stent ‘biocompatibility’ to prevent heart attack and improve long-term prognosis.
The Group focussed on exploring the role of potential therapeutic targets (specifically chemokines and high-density lipoproteins) by elucidating the molecular mechanisms involved in vascular complications associated with heart disease, including those involved in atherosclerotic plaque progression and impaired angiogenesis (new blood vessel formation). Additionally, work was also being done to improve stent biocompatibility and longevity.
Chemokines are small inflammatory proteins that play key roles in the body’s immune response to injury or infection. They direct the migration of inflammatory cells to sites of vascular injury and play a critical role in diseases such as atherosclerosis and inflammatory angiogenesis.
Another line of research assessed how high-density lipoproteins (HDL, or “good” cholesterol) might be used as a therapy to aid recovery and improve outcomes from stent implantation (an operation to open a blocked blood vessel). The Group also investigated how HDL regulates angiogenesis in diabetes, a condition in which angiogenesis is severely impaired.
The Immunobiology Group also had a strong interest in gene transfer technology, which involves using viruses to increase the levels of a protein of interest. The Group developed a number of different viral strategies to promote the levels of HDL and broad spectrum inhibitors of chemokines.
The focus of the Imflammation Group was to understand how reactive chemicals called oxidants, produced by the body during inflammation, can affect the function of blood vessels, to better understand the changes that occur in the arteries during the early stages of atherosclerosis.
Understanding changes that occur in the arteries during the early stages of atherosclerosis is vital to the rational development of new drugs and therapies to prevent this disease.
The Group was particularly interested in oxidants produced by an enzyme called myeloperoxidase, which is produced in the arteries by infiltrating immune cells during the inflammation. Myeloperoxidase is both a risk factor for coronary artery disease and a prognostic agent for patient outcome following cardiac complications, and is strongly associated with the development of atherosclerosis.