© 1999 American Heart Association, Inc.
Vascular Biology |
Lipoprotein-Associated Phospholipase A2, Platelet-Activating Factor Acetylhydrolase, Is Expressed by Macrophages in Human and Rabbit Atherosclerotic Lesions
Presented in part as preliminary results at the 69th Scientific Sessions of the American Heart Association, New Orleans, La, November 10–13, 1996, and published in abstract form (Circulation. 1996;94[suppl I]:I-585).
From A.I. Virtanen Institute (T.H., J.S.L., M.O.H., S.Y.-H.) and the Department of Medicine (J.S.L., S.Y.-H.), University of Kuopio, Kuopio, Finland; the Departments of Vascular Biology (C.H.M., K.J.M., L.P.), Gene Expression Sciences (S.Q.R.), and Molecular Recognition (D.G.T.), SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK; and Provincial State Office of Eastern Finland (K.K.), Kuopio, Finland.
Correspondence to Dr Seppo Ylä-Herttuala, MD, PhD, A.I. Virtanen Institute, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland. E-mail Seppo.YlaHerttuala{at}uku.fi
Abstract—We studied the
expression of lipoprotein-associated phospholipase A2
(Lp-PLA2), 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
lipoprotein, which plays an important role in atherogenesis, generates
biologically 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 and oxidized fatty acids released from
oxidized low-density lipoprotein as a result of Lp-PLA2
activity are thought to be involved in the progression of
atherosclerosis. Using combined in situ hybridization
and immunocytochemistry, we detected Lp-PLA2 mRNA and
protein in macrophages in both human and rabbit atherosclerotic
lesions. Reverse transcriptase—polymerase chain reaction
analysis indicated an increased expression of
Lp-PLA2 mRNA in human atherosclerotic lesions. In addition,
6-fold higher Lp-PLA2 activity was detected in
atherosclerotic aortas of Watanabe heritable
hyperlipidemic rabbits compared with normal aortas from
control rabbits. It is concluded that (1) macrophages in both
human and rabbit atherosclerotic lesions express Lp-PLA2,
which could cleave any oxidatively modified phosphatidylcholine
present in the lesion area, and (2) modulation of
Lp-PLA2 activity could lead to antiatherogenic effects in
the vessel wall.
Key Words: platelet-activating factor • atherogenesis • oxidized LDL • macrophages • real-time fluorescence polymerase chain reaction
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