Cabana VG

Chen GL

Clifton PM

Coetzee GA

Hosoai H


            Objective—
            Levels of serum amyloid A (SAA), an acute-phase protein carried on high-density lipoprotein (HDL), increase in inflammatory states and are associated with increased risk of cardiovascular disease. HDL colocalizes with vascular proteoglycans in atherosclerotic lesions. However, its major apolipoprotein, apolipoprotein A-I, has no proteoglycan-binding domains. Therefore, we investigated whether SAA, which has proteoglycan-binding domains, plays a role in HDL retention by proteoglycans.
          
          
            Methods and Results—
            HDL from control mice and mice deficient in both SAA1.1 and SAA2.1 (SAA knockout mice) injected with bacterial lipopolysaccharide (LPS) was studied. SAA mRNA expression in the liver and plasma levels of SAA increased dramatically in C57BL/6 mice after LPS administration, although HDL cholesterol did not change. Fast protein liquid chromatography analysis showed most of the SAA to be in HDL. Mass spectrometric analysis indicated that HDL from LPS-injected control mice had high levels of SAA1.1/2.1 and reduced levels of apolipoprotein A-I. HDL from LPS-injected control mice demonstrated high-affinity binding to biglycan relative to normal mouse HDL. In contrast, HDL from LPS-injected SAA knockout mice showed very little binding to biglycan, consistent with SAA facilitating the binding of HDL to vascular proteoglycans.
          
          
            Conclusion—
            SAA enrichment of HDL under inflammatory conditions plays an important role in the binding of HDL to vascular proteoglycans.
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Tsuyoshi Chiba

Mary Y. Chang

Shari Wang

Thomas N. Wight

Timothy S. McMillen

John F. Oram

Tomas Vaisar

Jay W. Heinecke

Frederick C. De Beer

Maria C. De Beer

Alan Chait

Crossref

Arteriosclerosis Thrombosis and Vascular Biology

Serum Amyloid A Facilitates the Binding of High-Density Lipoprotein From Mice Injected With Lipopolysaccharide to Vascular Proteoglycans

Serum Amyloid A Facilitates the Binding of High-Density Lipoprotein From Mice Injected With Lipopolysaccharide to Vascular Proteoglycans

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