We are interested in the genetics and molecular pathology of atherosclerosis, a complex multi-factorial vascular disease and the major cause of death and disabilities in the North America. Our approach consists of a series of experiments with mice carrying modifications in various genes specifying components important in lipid transport and clearance, and in genes important for the maintenance of vascular function and antioxidant defense. Using the spontaneous atherosclerosis in mice lacking apolipoprotein E as a basis, we have been studying interactions between genetic and environmental factors, and the effects on atherogenesis of other common disease conditions such as insulin resistance, diabetes and hypertension.