Human plasma platelet-activating factor acetylhydrolase binds to all the murine lipoproteins, conferring protection against oxidative stress.
OBJECTIVE
Plasma platelet-activating factor (PAF) acetylhydrolase (AH) is an enzyme bound with lipoproteins that degrades not only PAF but also PAF-like oxidized phospholipids that are proposed to promote atherosclerosis. In this study, we investigated the distribution of PAF-AH protein among lipoprotein classes by using adenovirus-mediated gene transfer in mice, and we examined its effects on lipoprotein oxidation and foam cell formation of macrophages.


RESULTS
Adenovirus-mediated overexpression of PAF-AH in mice resulted in a 76- to 140-fold increase in plasma PAF-AH activity. Contrary to the previous report, overexpressed human PAF-AH protein was bound to very low density lipoprotein, intermediate density lipoprotein, low density lipoprotein, and high density lipoprotein (HDL). All the lipoproteins with overexpressed human PAF-AH revealed more resistance against oxidative stress, which was associated with lower levels in autoantibody against oxidized low density lipoprotein in the plasma. In addition, HDL with human PAF-AH inhibited foam cell formation and facilitated cholesterol efflux in macrophages.


CONCLUSIONS
These results suggest that human plasma PAF-AH exerts an antiatherogenic effect by binding to all the lipoproteins and thereby protecting them from oxidation, producing less proatherogenic lipoproteins and preserving HDL functions.
Noto
Hiroshi
H
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Hara
Masumi
M
Karasawa
Ken
K
Iso-O
Naoyuki
N
Satoh
Hiroaki
H
Togo
Masako
M
Hashimoto
Yoshiaki
Y
Yamada
Yoshiji
Y
Kosaka
Tetsuya
T
Kawamura
Mitsunobu
M
Kimura
Satoshi
S
Tsukamoto
Kazuhisa
K
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000502:physiology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D001161:Arteriosclerosis / Q000517:prevention & control; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002478:Cells, Cultured / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D001057:Apolipoproteins E; D001323:Autoantibodies; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011993:Recombinant Fusion Proteins; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase