Abstract 1642: Feeding a Western Diet to LDL Receptor Null Mice Causes Inflammatory Changes in the Glomerulus, which are Ameliorated by D-4F an Apolipoprotein A-I Mimetic
Background- Feeding a Western diet to LDL receptor null mice results in hyperlipidemia, atherosclerosis, and endothelial dysfunction. Atheroslcerosis and endothelial dysfunction have been shown to be improved by oral administration of the apoA-I mimetic D-4F without altering hyperlipidemia. We asked if hyperlipidemia in this mouse model would result in renal glomerular changes and if D-4F would mitigate these changes.
Methods and Results- Female LDL receptor null mice were fed a Western diet for 6 to 8 weeks with D-4F (n =10) or the inactive control peptide, scrambled D-4F (ScD-4F) (n =10) added to their drinking water at 300 μg/mL. Kidneys were removed and the cellularity of the glomeruli and the ratio of the glomerulus to Bowman’s capsule (a measure of glomerular proliferation) were determined. Glomerular monocyte chemoattractant protein-1 (MCP-1) was quantified with Image Pro Plus software. Plasma lipids and lipoproteins were also determined and blood pressure was measured by the tail cuff method. The mice that received the inactive control peptide ScD-4F compared to D-4F had significantly more cells per glomerulus (62.8±1.9 cells per glomerulus for ScD-4F versus 37.2±0.8 for D-4F; p<0.0001). Consistent with these data the ratio of the glomerulus/Bowman’s capsule was significantly higher in the mice receiving the inactive control peptide ScD-4F compared to D-4F (0.87±0.01 for ScD-4F versus 0.82±0.01 for D-4F; p<0.005). The percent area stained in each glomerulus for MCP-1 was greater in mice receiving the inactive control peptide ScD-4F compared to D-4F (7.20±6.4 for ScD-4F versus 5.03±2.6 for D-4F; p<0.0001). There was no significant difference in plasma lipid or lipoprotein levels or in blood pressure.
Conclusion- Feeding a Western diet to LDL receptor null mice induces glomerular inflammation which is ameliorated by the apoA-I mimetic peptide D-4F without altering plasma lipids or blood pressure.