A study of hyperglycemia and its effects on endothelial activation, macrophage recruitment, and atherosclerotic plaque development in mice. Hyperglycemic mice demonstrated greater VCAM but not ICAM expression along the endothelium, increased macrophage presence within the subendothelial space of these regions, and a greater volume of plaque in adulthood. / Cardiovascular disease is the leading cause of death in the world today. Atherosclerosis is the formation of plaque in the arteries and a major underlying cause of these fatalities. Type I and II diabetes are each strong independent risk factors for atherosclerosis. This study examines the effects of hyperglycemia on early atherosclerosis. Hyperglycemia did not promote atherosclerosis in the absence of hypercholesterolemia. Hyperglycemic mice demonstrated greater VCAM, but not ICAM, expression in regions of the endothelium susceptible to atherogenesis, prior to initiation of plaque development. Regions correlating to upregulation of VCAM exhibited a greater quantity of macrophages infiltrating the intima. This study suggests a unique and important role for VCAM in early atherosclerotic development and may explain the accelerated atherosclerotic plaque progression seen in hyperglycemic mice. This study also identifies VCAM as a potential target for the development of therapies to block or slow atherosclerotic plaque development in people with diabetes. / Thesis / Master of Science (MSc) / Cardiovascular disease is the leading cause of death in the world today. A major underlying cause of cardiovascular disease is atherosclerosis – a condition involving the thickening of the artery wall. Type I and II diabetes are each strong independent risk factors for atherosclerosis. The purpose of this study is to examine the effects of high blood glucose (hyperglycemia) on early events leading to atherosclerosis. This study found that hyperglycemia was not sufficient to promote atherosclerosis unless plasma cholesterol levels were also elevated. Hyperglycemia appeared to induce atherosclerosis by increasing the expression of factors responsible for recruiting white blood cells to the artery wall. This is consistent with the observation that hyperglycemic mice also had significantly more macrophages in the sites of plaque development. This study implicates one macrophage-recruitment factor in particular, vascular cell adhesion molecule (VCAM), as playing an important and unique role in the initiation of atherosclerosis by hyperglycemia. Therefore, VCAM is a possible target for the development of therapies to block or slow the development of atherosclerosis in individuals with diabetes.