Grant: Operating Grant - PA: Regional Partnership Program - Newfoundland and Labrador

Heart disease is the leading cause of death in the Western world. The blockage of blood vessels is one of the major causes of this disease. The blockage is initiated by the uptake of blood fats carried by "bad cholesterol" (or LDL) into blood vessel walls. Existing medications are designed to reduce the levels of "bad cholesterol" and other bad fats in the blood. However, medications are also needed to promote both the removal of the cholesterol and bad fats from the vessel walls by "good cholesterol" (or HDL) and the removal of these fats from the body. The removal of the fats from blood vessels could slow disease progress or even reverse the blockage process. We will study an enzyme that might create more HDL in the blood from already existing HDL molecules. This enzyme, called hepatic lipase, breaks down fats on HDL. When this occurs, proteins fall off of HDL that can go on to make new smaller HDL molecules. Hepatic lipase is not normally free in the blood to carry out this process. Instead, hepatic lipase is normally bound to tissues such as the liver. We will design and test molecules that may specifically release hepatic lipase into the blood. Interruption of hepatic lipase binding should lead to the production of new smaller HDL. We will also test if the breakdown of fats from HDL by released hepatic lipase will result in the removal of the cholesterol and bad fats from cells that are typically found in blood vessel walls. Our engineered molecules may be used as a beneficial treatment against the initiation of blockages in blood vessels.