Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1284-1290
© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Role of Group II Secretory Phospholipase A2 in Atherosclerosis
1. Increased Atherogenesis and Altered Lipoproteins in Transgenic Mice Expressing Group IIa Phospholipase A2
From the Department of Microbiology and Molecular Genetics and Molecular Biology Institute (B.I., L.C., X.-P.W., J.-H.Q., M.M., A.J.L.), and the Department of Medicine, Division of Cardiology (B.I., L.C., X.-P.W., J.-H.Q., M.M., M.N., A.M.F., A.J.L.), University of California, Los Angeles; Chrysalis DNX Transgenic Sciences (D.S.G., M.E.S.), Princeton, New Jersey; and the Department of Internal Medicine and Biochemistry (M.C.d.B., F.d.B.), University of Kentucky, Lexington.
Correspondence to Aldons J. Lusis, Department Medicine, UCLA School of Medicine, Los Angeles, CA 90095.
Abstract—Some observations have suggested that the extracellular group IIa phospholipase A2 (sPLA2), previously implicated in chronic inflammatory conditions such as arthritis, may contribute to atherosclerosis. We have examined this hypothesis by studying transgenic mice expressing the human enzyme. Compared with nontransgenic littermates, the transgenic mice exhibited dramatically increased atherosclerotic lesions when maintained on a high-fat, high-cholesterol diet. Surprisingly, the transgenic mice also exhibited significant atherosclerotic lesions when maintained on a low-fat chow diet. Immunohistochemical staining indicated that sPLA2 was present in the atherosclerotic lesions of the transgenic mice. On both chow and atherogenic diets, the transgenic mice exhibited decreased levels of HDLs and slightly increased levels of LDLs compared with nontransgenic littermates. These data indicate that group IIa sPLA2 may promote atherogenesis, in part, through its effects on lipoprotein levels. These data also provide a possible mechanism for the observation that there is an increased incidence of coronary artery disease in many chronic inflammatory diseases.
Key Words: inflammation • lipoproteins • paraoxonase
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