Grant: Operating Grant - Priority Announcement: INMD Start Up Funds (bridge funding)

Atherosclerosis is a progressive disease in which fatty deposits build up within the arteries and interfere with the vital blood supply to body organs. It is at the origin of the majority of heart attacks and strokes that are the main cause of death worldwide. Atherosclerosis develops much faster upon exposure to high blood cholesterol in the form of low density lipoproteins (LDL), also called "bad" cholesterol. Fortunately, liver cells have a receptor that extracts LDL from the bloodstream thereby maintaining a healthy cholesterol level. However, due to several factors such as a familial history of elevated LDL, obesity or an unhealthy diet, over 10 millions of Canadians have an excess of cholesterol in the blood. Recently, a protein called PCSK9 was found to be a major cause of elevated blood cholesterol by continuously destroying the LDL receptor of the liver. Therefore, stopping the destructive activity of PCSK9 represents a very promising therapy to lower the level of "bad" cholesterol and the risk of premature atherosclerosis. Nonetheless, the mechanism by which PCSK9 induces the degradation of the LDL receptor is not well understood. Our previous observations and our preliminary data clearly indicate that other proteins can control the harmful activity of PCSK9. The main objective of our research project is to find and characterize these novel proteins in order to expand our scientific knowledge and to translate our discoveries into PCSK9 inhibitors for the prevention of cardiovascular diseases in the human population.