Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions

We studied the expression of lipoprotein-associated phospholipase A(2) (Lp- PLA(2)), an enzyme capable of hydrolyzing platelet-activating factor (PAF), PAF-like phospholipids, and polar-modified phosphatidylcholines, in human and rabbit atherosclerotic lesions. Oxidative modification of low-density l ipoprotein, which plays an important role in atherogenesis, generates biolo gically active PAF-like modified phospholipid derivatives with polar fatty acid chains. PAF is known to have a potent proinflammatory activity and is inactivated by its hydrolysis. On the other hand, lysophosphatidylcholine a nd oxidized fatty acids released from oxidized low-density lipoprotein as a result of Lp-PLA(2) activity are thought to be involved in the progression of atherosclerosis. Using combined in situ hybridization and immunocytoche mistry, we detected Lp-PLA(2) mRNA and protein in macrophages in both human and rabbit atherosclerotic lesions. Reverse transcriptase-polymerase chain reaction analysis indicated an increased expression of Lp-PLA(2) mRNA in h uman atherosclerotic lesions. In addition, approximate to 6-fold higher Lp- PLA(2) activity was detected in atherosclerotic aortas of Watanabe heritabl e hyperlipidemic rabbits compared with normal aortas from control rabbits. It is concluded that (1) macrophages in both human and rabbit atherosclerot ic lesions express Lp-PLA(2), which could cleave any oxidatively modified p hosphatidylcholine present in the lesion area, and (2) modulation of Lp-PLA (2) activity could lead to antiatherogenic effects in the vessel wall.