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

• Published in: Atherosclerosis Vol. 176; no. 1; pp. 37 - 44
• Main Authors: Khovidhunkit, Weerapan, Duchateau, Philippe N, Medzihradszky, Katalin F, Moser, Arthur H, Naya-Vigne, Josefina, Shigenaga, Judy K, Kane, John P, Grunfeld, Carl, Feingold, Kenneth R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01-09-2004; Elsevier
• Subjects: Acute-phase HDL; Acute-Phase Proteins - genetics; Acute-Phase Proteins - immunology; Acute-Phase Proteins - metabolism; Acute-phase response; Animals; Apolipoprotein A-V; Apolipoproteins - blood; Apolipoproteins - genetics; Apolipoproteins - immunology; Apolipoproteins A - blood; Apolipoproteins A - genetics; Apolipoproteins A - immunology; Arteriosclerosis - blood; Arteriosclerosis - immunology; Arteriosclerosis - physiopathology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood. Blood coagulation. Reticuloendothelial system; Carcinoma, Hepatocellular; Cardiology. Vascular system; Cell Line, Tumor; Cholesterol, HDL - blood; Cholesterol, HDL - immunology; Coronary heart disease; Endotoxin; Heart; Humans; Interleukin-6 - pharmacology; Lipopolysaccharide; Lipopolysaccharides - pharmacology; Liver - physiology; Medical sciences; Mice; Mice, Inbred C57BL; Pharmacology. Drug treatments; Proteomics; RNA, Messenger - metabolism; Acute-phase HDL; Lipopolysaccharide; Acute-phase response; Endotoxin; Proteomics; Rodentia; Cardiovascular disease; Lipopolysaccharide: Endotoxin; Vascular disease; Toxin; Apolipoprotein A; Vertebrata; Acute phase protein; Mammalia; Mouse; Animal; Atherosclerosis; Lipoprotein HDL
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2004.04.018

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 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.