366 - Serum Amyloid A Stimulates Atherogenesis and Renal Dysfunction in Apolipoprotein E-Deficient Mice Fed a Normal Chow Diet

Abstract

Elevated serum amyloid A (SAA) can cause endothelial dysfunction via enhanced oxidative stress that advances inflammation/thrombosis in cardiovascular and renal pathology. We investigated the impact of SAA on aortic vessels and renal function in apolipoprotein E-deficient (ApoE -/- ) mice. Male ApoE -/- mice received vehicle-(control), low-level lipopolysaccharide (LPS) or recombinant human SAA by i.p . injection every third day (over 2-weeks). Heart, aorta and kidney were harvested after 3 or 5 days, or after a total of 4 weeks (designated as young) or 18 weeks (old) mice. SAA-mediated-renal injury was evident in young mice manifesting as increased plasma blood nitrogen products, and urinary levels of protein and kidney injury molecule-1 (KIM-1), tissue content of oxidized lipids and several cytokines/chemokines, relative to controls. SAA stimulated NFκB activation and macrophage recruitment in kidneys as early as 3 days after administration. SAA increased vascular cell adhesion molecule (VCAM)-1 in aortic vessels and plasma monocyte chemotactic protein (MCP)-1 levels in young mice relative to their respective controls. Aortic gene expression of nuclear-factor-kappa-beta (NFκB-p50) and tissue factor (TF) also increased in young mice confirming that SAA stimulated pro-inflammatory/pro-thrombotic responses. These data suggest that SAA promotes renal impairment and endothelial dysfunction in ApoE -/- mice in the absence of a high-fat diet.