D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western diet.

Academic Article


  • LDL receptor-null (LDLR(-/-)) mice on a Western diet (WD) develop endothelial dysfunction and atherosclerosis, which are improved by the apolipoprotein A-I (apoA-I) mimetic peptide D-4F. Focusing on the kidney, LDLR(-/-)mice were fed a WD with D-4F or the inactive control peptide scrambled D-4F (ScD-4F) added to their drinking water. The control mice (ScD-4F) developed glomerular changes, increased immunostaining for MCP-1/CCL2 chemokine, increased macrophage CD68 and F4/80 antigens, and increased oxidized phospholipids recognized by the EO6 monoclonal antibody in both glomerular and tublo-interstitial areas. All of these parameters were significantly reduced by D-4F treatment, approaching levels found in wild-type C57BL/6J or LDLR(-/-) mice fed a chow diet. Sterol-regulatory element binding protein-1c (SREBP-1c) mRNA levels and triglyceride levels were elevated in the kidneys of the control mice (ScD-4F) fed the WD compared with C57BL/6J and LDLR(-/-) mice on chow (P < 0.001 and P < 0.001, respectively) and compared with D-4F-treated mice on the WD (P < 0.01). There was no significant difference in plasma lipids, lipoproteins, glucose, blood pressure, or renal apoB levels between D-4F- and ScD-4F-treated mice. We conclude that D-4F reduced renal oxidized phospholipids, resulting in lower expression of SREBP-1c, which, in turn, resulted in lower triglyceride content and reduced renal inflammation.
  • Published In


  • Animals, Antibodies, Monoclonal, Apolipoprotein A-I, Diet, Female, Inflammation, Kidney, Lipid Metabolism, Mice, Oxidation-Reduction, Phospholipids, RNA, Messenger, Receptors, LDL, Sterol Regulatory Element Binding Protein 1, Triglycerides
  • Digital Object Identifier (doi)

    Author List

  • Buga GM; Frank JS; Mottino GA; Hakhamian A; Narasimha A; Watson AD; Yekta B; Navab M; Reddy ST; Anantharamaiah GM
  • Start Page

  • 192
  • End Page

  • 205
  • Volume

  • 49
  • Issue

  • 1