Whereas aldose reductase deletion (global) enhances atherosclerotic plaque in the hypercholesterolemic ApoE-null mouse on high-fat diet as well as in streptozotocin-induced diabetes [210], general and endothelial targeted overexpression of human AR in models of hypercholesterolemia also showed enhanced plaque size in diabetic animals [211, 212]. This evidence concerns the gene AKR1B1 and diabetes mellitus.