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.


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 A-V as positive acute-phase proteins in mouse HDL. We also found an increase in hepatic mRNA levels of apo A-IV and apo A-V after injection of endotoxin. Interleukin-6 increased apo A-IV and apo A-V 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 A-V 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 A-V, 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.
Metabolism Section, Department of Veterans Affairs Medical Center, 4150 Clement Street, Box 111 F, San Francisco, CA 94121, USA.
Weerapan
W
Khovidhunkit
Philippe N
PN
Duchateau
Katalin F
KF
Medzihradszky
Arthur H
AH
Moser
Josefina
J
Naya-Vigne
Judy K
JK
Shigenaga
John P
JP
Kane
Carl
C
Grunfeld
Kenneth R
KR
Feingold
D000209:Acute-Phase Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000097:blood / Q000235:genetics / Q000276:immunology; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001161:Arteriosclerosis / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D008076:Cholesterol, HDL / Q000097:blood / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism
C437704:APOA5 protein, human; D000209:Acute-Phase Proteins; C499058:Apoa5 protein, mouse; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C022205:apolipoprotein A-IV