Apolipoproteins A-IV and A-V are acute-phase proteins in mouse HDL

Background: Infection and inflammation are associated with atherosclerosis. During infection and inflammation, HDL decreases and there are changes in the levels of several HDL-associated proteins. To identify changes in the protein composition of HDL during infection and inflammation, a proteomic approach was utilized. Methods and results: Using two-dimensional gel electrophoresis and mass spectrometry, we found the expected increases in apolipoprotein (apo) SAA and apo E. as well as a decrease in apo A-I on HDL isolated from mice injected with endotoxin. We identified apo A-IV and apo AN as positive acute-phase proteins in mouse HDL. We also found an increase in hepatic mRNA levels of apo A-IV and apo AN after injection of endotoxin. Interleukin-6 increased apo A-IV and apo AN mRNA levels in Hep3B cells. Additionally, we demonstrated that the protein levels of apo A-II in acute-phase HDL and the hepatic mRNA levels of apo A-II were decreased. Conclusions: Apo A-IV and AN are positive acute-phase proteins that increase in the serum during inflammation while apo A-II is a negative acute-phase protein in mice. Similar to other positive and negative acute-phase proteins, changes in hepatic production account for the changes in serum levels. However, the changes in apo A-IV and apo AN, two apolipoproteins whose activities are not fully understood, may serve functions other than regulating lipid metabolism during the acute-phase response (APR). Coupled with the other changes in HDL proteins that occur, these changes are likely to alter the functional properties of HDL perhaps increasing the risk of atherosclerosis. (C) 2004 Elsevier Ireland Ltd. All rights reserved.