Role of Group II Secretory Phospholipase A₂in Atherosclerosis

TLDR

Extracellular group IIa phospholipase A2, implicated in chronic inflammatory diseases, has been suggested to contribute to atherosclerosis. The study aimed to test whether sPLA2 promotes atherosclerosis. This was investigated using transgenic mice that express the human sPLA2 enzyme. Transgenic mice displayed markedly larger atherosclerotic lesions on both high‑fat and low‑fat diets, with sPLA2 present in lesions, reduced HDL, slightly increased LDL, supporting a role for sPLA2 in atherogenesis partly via lipoprotein alterations and providing a mechanistic link to coronary disease in inflammatory conditions.

Abstract

Abstract —Some observations have suggested that the extracellular group IIa phospholipase A 2 (sPLA 2 ), 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 sPLA 2 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 sPLA 2 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.