Targeting efferocytosis to reduce risk of cardiovascular events

Heart attack and stroke are the leading causes of death in Canada. These lethal events are caused by diseased cells accumulated on the wall of the blood vessels, leading to narrowing of the arteries. Although diseased cells can be removed naturally, this process is inhibited by inflammation. Recently, anti-inflammatory drugs are being actively developed to reduce heart attacks, but we lack methods to assess their effectiveness before testing in patients. This problem led to the failure of several clinical trials and serious side effects due to non-specific inhibition of the immune system. We will use models that closely mimic the conditions of patients and apply a thorough “onsite inventory” of diseased arteries to: 1) understand how inflammation inhibits the removal of diseased cells; 2) see if current drug candidates can neutralize these adverse effects in diseased arteries; and 3) explore and develop markers that can find patients who will benefit from the drug candidates. This study will provide evidence to guide the design of more specific anti-inflammatory drugs and their application to the right patients. It will minimize side effects and allow more patients to be properly treated to prevent heart attacks and strokes.