Impact of serum amyloid A on high density lipoprotein composition and levels

Maria C De Beer,Nancy R Webb,Joanne M Wroblewski,Victoria P Noffsinger,Debra L Rateri,Ailing Ji,Deneys R Van Der Westhuyzen,Frederick C De Beer

doi:10.1194/jlr.m005413

Maria C De Beer, Nancy R Webb + Show 6 more

Open Access

https://doi.org/10.1194/jlr.m005413

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Abstract

Serum amyloid A (SAA) is an acute-phase protein mainly associated with HDL. To study the role of SAA in mediating changes in HDL composition and metabolism during inflammation, we generated mice in which the two major acute-phase SAA isoforms, SAA1.1 and SAA2.1, were deleted [SAA knockout (SAAKO) mice], and induced an acute phase to compare lipid and apolipoprotein parameters between wild-type (WT) and SAAKO mice. Our data indicate that SAA does not affect apolipoprotein A-I (apoA-I) levels or clearance under steady-state conditions. HDL and plasma triglyceride levels following lipopolysaccharide administration, as well as the decline in liver expression of apoA-I and apoA-II, did not differ between both groups of mice. The expected size increase of WT acute-phase HDL was surprisingly also seen in SAAKO acute-phase HDL despite the absence of SAA. HDLs from both mice showed increased phospholipid and unesterified cholesterol content during the acute phase. We therefore conclude that in the mouse, SAA does not impact HDL levels, apoA-I clearance, or HDL size during the acute phase and that the increased size of acute-phase HDL in mice is associated with an increased content of surface lipids, particularly phospholipids, and not surface proteins. These data need to be transferred to humans with caution due to differences in apoA-I structure and remodeling functions.

Highlights

Serum amyloid A (SAA) is an acute-phase protein mainly associated with acute-phase HDL (HDL)
Because the liver is the main site of apolipoprotein synthesis, we examined the hepatic expression of the major HDL apolipoproteins, apolipoprotein A-I (apoA-I), apoA-II, and SAA by quantitative RT-PCR
We explored the role that acute-phase SAA could play in the altered lipoprotein profiles characteristic of inflammation [2, 3, 17]

Summary

Introduction

Serum amyloid A (SAA) is an acute-phase protein mainly associated with HDL. To study the role of SAA in mediating changes in HDL composition and metabolism during inflammation, we generated mice in which the two major acute-phase SAA isoforms, SAA1.1 and SAA2.1, were deleted [SAA knockout (SAAKO) mice], and induced an acute phase to compare lipid and apolipoprotein parameters between wild-type (WT) and SAAKO mice. We conclude that in the mouse, SAA does not impact HDL levels, apoA-I clearance, or HDL size during the acute phase and that the increased size of acute-phase HDL in mice is associated with an increased content of surface lipids, phospholipids, and not surface proteins. These data need to be transferred to humans with caution due to differences in apoA-I structure and remodeling functions.—de Beer, M. Data indicated that the absence of SAA does not influence plasma lipid or HDL levels during inflammation or the clearance of apoA-I under steady-state conditions.

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