Lipoprotein inflammatory properties and serum amyloid A levels but not cholesterol levels predict lesion area in cholesterol-fed rabbits

Brian J Van Lenten,Alan C Wagner,Mohamad Navab,G.M Anantharamaiah,Susan Hama,Srinivasa T Reddy,Alan M Fogelman

doi:10.1194/jlr.m700138-jlr200

Abstract

Rabbits on a 1% cholesterol diet received injections of vehicle with or without D-4F or L-4F. After 1 month, the percent of aorta with atherosclerotic lesions was 24 +/- 15% (vehicle), 10 +/- 6% (D-4F) (P < 0.01 vs. vehicle), and 13 +/- 9% (L-4F) (P < 0.05 vs. vehicle). Inflammatory indexes for HDL and LDL were determined by measuring monocyte chemotactic activity after adding rabbit lipoproteins to human endothelial cells. HDL-inflammatory index (HII) and LDL-inflammatory index (LII), respectively, were 1.39 +/- 0.24; 1.35 +/- 0.29 (vehicle), 0.67 +/- 0.26; 0.63 +/- 0.38 (D-4F) (P < 0.001 vs. vehicle), and 0.67 +/- 0.2; 0.68 +/- 0.32 (L-4F) (P < 0.01 vs. vehicle). Serum amyloid A (SAA) levels were 95 +/- 39, 8 +/- 22, and 7 +/- 19 mug/ml, respectively, for vehicle, D-4F, and L-4F (P < 0.001 vs. vehicle). There was no correlation between lesion area and total plasma or HDL-cholesterol levels. In contrast, there was a positive correlation with HII, LII, and SAA (P = 0.002, P = 0.0026, P = 0.0079, respectively). HII correlated closely with SAA levels (r = 0.6616; r(2) = 0.4377, P < 0.0001). Thus, HII, LII, and SAA are better predictors of lesion area than are total plasma or HDL-cholesterol levels in cholesterol-fed rabbits.

Highlights

Incubation of the peptides in vitro with pooled plasma from fasted rabbits after 1 month on the 1% cholesterol diet but before treatment was started did not cause any significant changes in the fast protein liquid chromatography (FPLC) cholesterol profile of the apoBcontaining lipoproteins, suggesting that the change in profile seen in vivo was not due to a direct action of the peptides on the apoB-containing lipoproteins
The inflammatory indices of the lipoproteins and Serum amyloid A (SAA) levels correlated better with lesion area than the plasma lipoprotein levels did, we do not exclude a contribution to the decrease in lesion area with peptide treatment, inasmuch as there was a significant decrease in apoB-containing lipoproteins with peptide treatment compared with vehicle treatment
These data further establish the relationship between inflammation as measured by SAA levels and lesion area in cholesterol-fed rabbits and are consistent with the results of Lewis et al [20], who found that SAA levels predicted lesion area in LDL receptor-null mice fed a highcholesterol, high-fat diet

Summary

Introduction

Incubation of the peptides in vitro with pooled plasma from fasted rabbits after 1 month on the 1% cholesterol diet but before treatment was started did not cause any significant changes in the FPLC cholesterol profile of the apoBcontaining lipoproteins (data not shown), suggesting that the change in profile seen in vivo was not due to a direct action of the peptides on the apoB-containing lipoproteins.

Results

Conclusion