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Journal of Lipid Research, Vol. 48, 2344-2353, November 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

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

Brian J. Van Lenten^1,*, Alan C. Wagner^*, Mohamad Navab^2,*, G. M. Anantharamaiah^2,, Susan Hama^2,*, Srinivasa T. Reddy^2,*, and Alan M. Fogelman^2,*

^* Department of Medicine, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095-1679
Atherosclerosis Research Unit, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095-1679

Published, JLR Papers in Press, August 10, 2007.

² M. Navab, S. T. Reddy, S. Hama, G. M. Anantharamaiah, and A. M. Fogelman are principals in Bruin Pharma, and A. M. Fogelman is an officer in Bruin Pharma.

¹ To whom correspondence should be addressed. e-mail: bvanlent{at}mednet.ucla.edu

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 µg/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; r² = 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.

Supplementary key words atherosclerosis • LDL • HDL • apolipoprotein A-I mimetic peptides • inflammation

Abbreviations: apoA-I, apolipoprotein A-I; FPLC, fast protein liquid chromatography; HII, HDL-inflammatory index; LII, LDL-inflammatory index; MCP-1, monocyte chemoattractant protein-1; SAA, serum amyloid A

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