Figure 4: Effects of D-4F treatment in streptozotocin-induced diabetic mice. The induction of diabetes in mice results in hyperglycemia-mediated generation of reactive oxygen species and advanced glycosylation end products. These changes create a systemic inflammatory state that promotes endothelial damage and atheroma formation. Many of these deleterious effects were either diminished or reversed following treatment with apolipoprotein mimetic peptide D-4F. Treatment with D-4F has a vascular protective effect as evidenced by decreased endothelial sloughing and increased thrombomodulin formation, a marker of endothelial cell function. The increase in heme oxygenase 1 (HO-1) and extracellular superoxide dismutase (EC-SOD) helps prevent uncoupling of endothelial nitric oxide synthase and reactive oxygen species formation, leading to improved vasoreactivity and vascular repair. D-4F mediated prevention of atherosclerosis development is associated with a reduction in lipid and macrophage content of the atherosclerotic lesions. Abbreviations: ECSOD, extracellular superoxide dismutase; HO-1, heme oxygenase 1.