Human Plasma Platelet-Activating Factor Acetylhydrolase Binds to All the Murine Lipoproteins, Conferring Protection Against Oxidative Stress

H. Noto
2003 Arteriosclerosis, Thrombosis and Vascular Biology  
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. Methods and Results-Adenovirus-mediated
more » ... denovirus-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. (Arterioscler Thromb Vasc Biol. 2003;23:829-835.)
doi:10.1161/01.atv.0000067701.09398.18 pmid:12649088 fatcat:smh35h3pxzgujexcu5rj2egh5y