Abstract 383: Lack of Endogenous Acute Phase Serum Amyloid A Does Not Impact Atherosclerotic Lipid Deposition in ApoE-/- Mice.

Abstract

Inflammation is involved in all stages of the development of an atherosclerotic plaque. Serum amyloid A (SAA), a marker of inflammation, is a well-known predictor of increased cardiovascular risk. Although elevated levels of plasma SAA have been associated with increased atherosclerosis, the role of SAA in the pathogenesis of atherosclerosis remains obscure. To investigate the impact of endogenous SAA in the etiology of atherosclerosis we bred mice lacking both major acute phase SAA isoforms SAA1.1 and SAA2.1 to apoE-/- mice. Both strains were in the C57BL/6 background. For ease of terminology we refer to these mice as SAAKO and apoE-/- mice. Aortic atherosclerotic lesion areas were quantified by en face analysis in male and female mice fed normal chow for 12 months. Although female mice weighed less and had lower plasma lipid levels than male mice, the absence of SAA did not affect plasma lipid concentrations or lipoprotein-cholesterol profiles or the size of aortic atherosclerotic lesions of apoE-/- mice. To accelerate lesion formation, male and female apoE-/- and SAAKO mice were fed a Western diet for 12 weeks. We observed gender-related differences in body weight, weight gain and plasma lipid concentrations. However, absence of SAA in apoE-/- mice fed a diet enriched in saturated fat had no discernable effect on plasma lipid concentrations, lipoprotein-cholesterol profiles or the size of the aortic atherosclerotic lesions. Lesions in the aortic root of male mice, quantitated by oil red O staining, was also not affected by genotype. We conclude that absence of endogenous acute phase SAA does not impact atherosclerotic lesion development in apoE-/- mice fed normal or fat-enriched diets.