Role of group II secretory phospholipase A(2) in atherosclerosis - 1. Increased atherogenesis and altered lipoproteins in transgenic mice expressing group IIa phospholipase A(2)

Some observations have suggested that the extracellular group IIa phospholi pase A(2) (sPLA(2)), previously implicated in chronic inflammatory conditio ns such as arthritis, may contribute to atherosclerosis. We have examined t his hypothesis by studying transgenic mice expressing the human enzyme. Com pared with nontransgenic littermates, the transgenic mice exhibited dramati cally increased atherosclerotic lesions when maintained on a high-fat, high -cholesterol diet. Surprisingly, the transgenic mice also exhibited signifi cant atherosclerotic lesions when maintained on a low-fat chow diet. Immuno histochemical staining indicated that sPLA(2) was present in the atheroscle rotic lesions of the transgenic mice. On both chow and atherogenic diets, t he transgenic mice exhibited decreased levels of HDLs and slightly increase d levels of LDLs compared with nontransgenic littermates. These data indica te that group IIa sPLA(2) may promote atherogenesis, in part, through its e ffects 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.