Platelet-Activating Factor Acetylhydrolase Is Mainly Associated With Electronegative Low-Density Lipoprotein Subfraction

Abstract

Background— Electronegative LDL [LDL(−)], a modified subfraction of LDL present in plasma, induces the release of interleukin-8 and monocyte chemotactic protein-1 from cultured endothelial cells. Methods and Results— We demonstrate that platelet-activating factor acetylhydrolase (PAF-AH) is mainly associated with LDL(−). LDL(−) had 5-fold higher PAF-AH activity than the nonelectronegative LDL subfraction [LDL(+)] in both normolipemic and familial hypercholesterolemic subjects. Western blot analysis after SDS-PAGE confirmed these results, because a single band of 44 kDa corresponding to PAF-AH appeared in LDL(−) but not in LDL(+). Nondenaturing polyacrylamide gradient gel electrophoresis demonstrated that PAF-AH was bound to LDL(−) regardless of LDL size. In accordance with the above findings, nonesterified fatty acids, a cleavage product of PAF-AH, were increased in LDL(−) compared with LDL(+). Conclusions— The high PAF-AH activity observed in LDL(−) could be related to the proinflammatory activity of these lipoproteins toward cultured endothelial cells.