Targeting apolipoprotein C3 to reduce cardiovascular risk

Atherosclerosis, the process by which fats, cholesterol and other substances build up in the artery wall, is the leading cause of CV disease. This process begins as early as the teen years and continues throughout life. Preventing transition of plaques to an advanced or rupture-prone state that cause most of the fatal events, represents the best opportunity for impact. We have identified that targeting the protein apolipoprotein C3 (apoC3), found on the surface of lipoproteins and involved in triglyceride metabolism, has the potential to reduce plaque transition. As lipoproteins circulate in the blood, apoC3 is constantly in contact with the vascular wall, and our preliminary observations suggest that the pro-inflammatory effects of apoC3 can cause direct damage to the vascular wall lining (endothelium). Inflammation of the endothelium accelerates the progression of atherosclerotic plaque formation. It is now evident that at least a third of CV disease cases have an inflammatory basis. This makes apoC3 an exciting therapeutic target for reducing CV risk. We hypothesise that apoC3 has a direct, deleterious role in the vascular wall that promotes inflammation and leads to vascular complications including atherosclerosis. During this PhD you will investigate the role of apoC3 in vascular inflammation with a series of translational studies designed to both understand the mechanisms and identify a therapeutic solution. The key aims are to determine: 1. The role of apoC3 in atherosclerosis and plaque vulnerability. 2. The inflammatory mechanisms underlying a damaging role of apoC3 in the vascular wall. 3. The impact of apoC3 on the vascular complications of diabetes. 4. The potential for apoC3 to predict patients at an increased CV risk. Our laboratory are ideally placed to support you to undertake this translational project, with expertise in validating novel therapeutics in pre-clinical cell and animal models of atherosclerosis and diabetes, and access to advanced imaging data from established CV clinical cohorts. This project will be conducted in the Biomedicine Discovery Institute and the brand new Victorian Heart Hospital, with access to state of the art labs and techniques. By demonstrating the importance of apoC3 as a therapeutic target, we will pave the way to reducing atherosclerotic disease.