Grant: Operating Grant

Cardiovascular disease (CVD), including heart disease, stroke and peripheral vascular disease, is the leading cause of death in Canada and in Western society. When death is not the end point, CVD jeopardized the quality of life. CVD is also the leading cause of hospital admissions and despite progress in its prevention, detection, and treatment, which exact an enormous toll in Canada, it will still kill thousand of Canadian this year. Several risk factors for coronary artery disease (CAD) have been well documented including gender, age, hyperlipidemia, hypertension, smoking, diabetes, family history, physical inactivity, overweight and excessive alcohol. However these factors explain only part of attributable CVD, and other factors must be involved. Indeed, a growing body of evidence supports the concept that local and systemic chronic inflammation may play a role in the initiation and progression of atherosclerosis and its complication (angina crisis, stroke and sudden death). In the arteries, atherosclerosis is characterized by a recruitment of cells of the immune system into the vessel wall, an accumulation of circulating cholesterol followed by an increase in the number of vascular muscle cells, the major component of the vascular system. These processes lead ultimately to plaque formation, which diminish blood flow and ultimately leads to myocardial infarction or stroke. The underlying cause of this chronic inflammation and how its specifically relates to CAD is at the moment unknown. Evidence generated by our group of research now suggests that a class of enzymes know as E3 ubiquitin ligases might be involved in chronic inflammation reaction present in the vasculature. This research proposal will therefore address the role of a master regulator of inflammatory reactions, the E3 ligases TRAF6, in vascular growth and inflammation as well as atherosclerosis development by the generation of a novel transgenic mice model.