Head – Dmitri Sviridov
Working toward the development of therapeutics to treat atherosclerosis and reduce the incidence of cardiovascular diseases
It is well documented that cholesterol can be a problem when there is too much of it in the blood, potentially leading to the development of many cardiovascular diseases. The research undertaken by Dmitri Sviridov and his team at Baker IDI aims understand and address this problem by investigating the metabolism of cholesterol and the mechanisms responsible for its accumulation.
Lipoproteins carry cholesterol throughout the bloodstream. Just like oil and water, cholesterol and blood do not mix. In order to be able to travel in the bloodstream, cholesterol is combined with protein to form lipoproteins. Lipoproteins are also responsible for the accumulation of cholesterol in the blood. This accumulated cholesterol causes fatty deposits to build up in the blood vessel wall, this is known as atherosclerosis.
In the last 10 years, statins, together with maintaining a healthy lifestyle, have been the most effective therapy in treating atherosclerosis by reducing the delivery of cholesterol to the vessel wall. This therapy has been effective in decreasing the incidence of heart disease by as much as 30 per cent. For the remaining 70 per cent whose lives are not saved by statins and maintaining a healthy lifestyle, the research by Dmitri and his team is crucial.
The lipoproteins and atherosclerosis laboratory is investigating the body’s natural protective mechanism process which removes excess cholesterol from the vessel wall. This mechanism is dependent on two functions, the cells ability to transfer excess cholesterol to the plasma, and the plasma’s capacity to receive excess cholesterol from the cells. Understanding how these functions work, why and how the protective mechanism process breaks down and how to supplement this mechanisms if its activity is insufficient will assist in the development of therapeutics which will restore this process in patients where it is impaired or no longer working.
One of the lab’s most significant ongoing projects investigates the development of atherosclerosis in patients with HIV. Advanced treatments in HIV have seen patients living longer lives, and as a result it has become evident that these patients have a higher incidence of heart disease than other members of the community. It was always believed that this higher incidence rate was due to adverse effects of the HIV treatment, as these drugs are known to increase cholesterol in the plasma. However, Dmitri’s lab found the HIV virus itself actually shuts down the body’s protective mechanism process to such an extent that cells infected with HIV begin accumulating cholesterol making it impossible for them to transfer excess cholesterol to the plasma. The plasma’s capacity to receive excess cholesterol from these cells is also significantly affected. In addition it was also found that if the pathway that is causing HIV infected cells to accumulate cholesterol can be controlled, this will not only reduce the development of atherosclerosis in the patient, but will also reduce the activity of the HIV virus.