Grant: Operating Grant

Heart disease accounts for the majority of deaths in North America. Acute clinical manifestations of heart disease result from the rupture of atherosclerotic lesions, resulting in blood clots and vessel blockage. Programmed cell death has been well documented in animal and human atherosclerotic lesions, and contributes to lesion rupture and clot formation. Although cell death influences lesion growth, stability and clot formation, the cellular mechanisms and/or factors responsible for this effect are incompletely understood. We have reported that a specific cellular factor, termed T-cell death associated gene 51 (TDAG51), causes cell death and contributes to atherosclerotic lesion development. Our findings demonstrate increased expression of TDAG51 within lesion resident endothelial cells and macrophages. Furthermore, deficiency in TDAG51 causes a significant reduction in atherosclerotic lesion development in established mouse models of atherogenesis. The overall objective of this research proposal is to better understand how TDAG51 contributes to the development and progression of heart disease. The findings from this research project will allow us to better understand the role of TDAG51 and to develop novel therapeutic stategies for the treatment/prevention of heart disease.