Role of secretory phospholipases in atherogenesis

Elevated circulating levels of secretory phospholipase A₂ (sPLA₂) are associated with atherosclerotic cardiovascular disease. sPLA₂ can contribute to atherogenesis by hydrolyzing phospholipids of circulating lipoproteins and lipoproteins entrapped in the arterial wall and/or in cells that reside in the intima and that participate in the inflammatory response to lipoprotein deposition. This article reviews differences and similarities between sPLA₂-IIA, sPLA₂-V, and sPLA₂-X, all of which are members of this family of enzymes with reported potential proatherogenic features. Published data suggest that each of the enzymes has a distinct profile characterized by differences in tissue expression and localization, capacity to act on phospholipids of cell membranes and lipoproteins, and their interaction with arterial proteoglycans. In addition, the article discusses results from the authors’ laboratory showing that diet-induced or gene-induced hyperlipidemia in mice enhances the expression of sPLA₂-V in different tissues, but not sPLA₂-IIA. Such differences indicate that these enzymes may have different roles in atherosclerotic cardiovascular disease through their distinct profiles.