Atherothrombotic Disease

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Detecting and Treating Atherothrombotic Disease McMaster researchers have developed a method for the detection and prevention of atherothrombotic disease. This method is based on the discovery that anti-GRP78 autoantibodies in the bloodstream can accelerate atherosclerotic lesion development and increase the activity of tissue factor, the key cellular initiator of blood coagulation. Abstract Heart disease and stroke are major causes of death and morbidity in Canada and they extract high personal, community and health care costs. Most heart attacks and strokes are caused by thrombus formation superimposed on disrupted atherosclerotic plaques, a process known as atherothrombosis. A number of risk factors are known to accelerate atherothrombosis including hypercholesterolemia, smoking, diabetes, hypertension, obesity and hyperhomocysteinemia. McMaster researchers have developed a method for the detection and prevention of atherothrombotic disease. This method is based on the discovery that anti-GRP78 autoantibodies in the bloodstream can accelerate atherosclerotic lesion development and increase the activity of tissue factor, the key cellular initiator of blood coagulation. Specifically, our researchers have demonstrated that: (i) serum levels of GRP78 autoantibodies increase with the progression of atherosclerosis in a mouse model of accelerated atherosclerosis, and (ii) atherosclerotic lesion development is significantly accelerated in apoE10 deficient mice having increased anti-GRP78 autoantibody titres Accordingly, eliminating, disrupting or neutralizing these anti-GRP78 autoantibodies from interacting with cell surface GRP78 on cell types relevant to plaque development can be used to treat or prevent atherothrombotic disease and its complications. Applications Potential biomarkers for the diagnosis of cardiovascular disease Novel mechanism that explains the link between blood levels of anti-GRP78 autoantibodies Therapeutic target for reducing the risk of cardiovascular disease and its thrombotic complications Advantages Provides a direct and unique connection between anti-GRP78 autoantibodies and the progression of atherothrombotic disease Explains the connection between the expression of cell surface GRP78 on endothelial cells and the increased blood levels of autoantibodies to GRP78 Tech ID 10-045 Inventors R. Austin Patent Status US Provisional filed Stage of Research Murine studies continue to verify that peptides known to bind to anti-GRP78 auto-antibodies prevent the development of atherothrombotic disease.