Grant: Project Grant

Cardiovascular diseases are the number one killer in Canada. The current therapy for preventing and treating atherosclerosis (stiffening and blocking of arteries) uses statins to reduce levels of LDL (bad) cholesterol in the blood. Statins reduce cardiovascular events by 20% to 40%. A potentially more effective therapy was recently approved, using antibodies that block the action of the enzyme PCSK9. This enzyme interferes with removing LDL cholesterol from the blood. However, this is a costly strategy that requires injections of large amounts of antibody for clinical effectiveness, limiting the wide use of these drugs. Given that more than 50,000 strokes and 75,000 heart attacks occur in Canada every year, the need for new cardiovascular therapies is clear and urgent. Recently, we found that the protein MMP14 reduces the levels of a protein called the LDL receptor that is critical for clearing LDL cholesterol from the blood. Blocking the action of MMP14 increases levels of the LDL receptor and reduces LDL cholesterol in blood. In this project we will characterize MMP14 and determine how it works when it reduces levels of the LDL receptor. This basic knowledge will open up new opportunities for blocking MMP14 and reducing LDL cholesterol in blood. This knowledge can offer more effective and perhaps less expensive avenues to treat patients with increased risk of cardiovascular disease.