ABCG1 is a novel ABC transporter that is present on macrophages and is a primary regulator of cholesterol[unreadable] efflux from macrophages to HDL in reverse cholesterol transport. Major unresolved questions in the field of[unreadable] atherosclerosis are whether ABCG1 directly regulates macrophage foam cell formation and thus, whether[unreadable] ABCG1 significantly influences atherosclerosis development. We have recently discovered in our laboratory[unreadable] that ABCG1 expression is dramatically downregulated in diabetic mouse macrophages, and that this ABCG1[unreadable] downregulation decreases macrophage cholesterol efflux, thereby increasing foam cell formation in diabetic[unreadable] mice. Incidence of atherosclerosis is accelerated in patients with both type 1 and Type 2 diabetes 1"10.[unreadable] Recent work by Peter Edwards and colleagues showed that mice lacking ABCG1 had significant lipid[unreadable] deposition in multiple tissues, including both macrophages and endothelial cells11. Although atherosclerosis[unreadable] studies have not yet been performed in the ABCG1-deficient mice, the phenotypic profile of gross lipid[unreadable] accumulation in the animals strongly suggests that ABCG1 will be an important regulator of atherosclerosis[unreadable] development. In the current application, we hypothesize that chronic hyperglycemia in diabetes decreases[unreadable] macrophaqe ABCG1 function and results in increased macrophage foam cell formation in vivo. We[unreadable] hypothesize that the reduction in macrophage ABCG1 function increases atherosclerosis in the setting of[unreadable] diabetes. We propose to study how glucose regulates ABCG1 expression and function in diabetes.