Reduction in ABCG1 in Type 2 Diabetic Mice Increases Macrophage Foam Cell Formation*

Atherosclerosis development is accelerated severalfold in patients with Type 2 diabetes. In the initial stages of disease, monocytes transmigrate into the subendothelial space and dif-ferentiate into foam cells. Scavenger receptors andATPbinding cassette (ABC) Transporters play an important role in foam cell formation as they regulate the influx and efflux of oxidized lip-ids. Here, we show that peritoneal macrophages isolated from Type 2 diabetic db/db mice have decreased expression of the ABC transporter ABCG1 and increased expression of the scav-enger receptor CD36. We found a 2-fold increase in accumula-tion of esterified cholesterol in diabetic db/db macrophages compared with wild-type control macrophages. Diabetic db/db macrophages also had impaired cholesterol efflux to high den-sity lipoprotein but not to lipid-free apo A-I, suggesting that the increased esterified cholesterol in diabetic db/dbmacrophage