Secretory phospholipase A2 enzymes in atherogenesis

Purpose of review Immunohistochemistry studies have confirmed the presence of group IIA, group V and group X secretory phospholipase A(2) in human or mouse atherosclerotic lesions. The possibility that secretory phospholipase A(2) plays a role in the pathophysiology of atherosclerosis (and is not merely a marker for localized inflammation) has been substantiated by a number of recent in-vitro and in-vivo studies. Recent findings A mouse strain with a targeted deletion of group V secretory phospholipase A(2) has been developed. Peritoneal macrophages from these mice have significantly blunted eicosanoid generation in response to zymosan, providing the first direct evidence that a secretory phospholipase A(2) plays a role in stimulation-induced arachidonic acid production in vivo. A recent in-vitro study indicated that de novo synthesized groups IIA and X secretory phospholipase A(2) can mediate arachidonic acid release intracellularly, without the requirement for previous secretion from cells, as was previously thought. Several studies support the previously proposed model that secretory phospholipase A(2) hydrolysis generates pro-atherogenic LDL. These data, coupled with the finding that macrophage-specific expression of human group IIA secretory phospholipase A(2) promotes atherosclerotic lipid deposition in mice, draw attention to secretory phospholipase A(2) as an attractive target for the treatment of atherosclerotic disease. Summary Secretory phospholipase A(2) activity in the arterial intima has the potential to amplify atherogenic processes by liberating potent pro-inflammatory lipid mediators and by generating pro-atherogenic LDL Future in-vivo studies will aid in defining the mechanism(s) that underlie the pro-atherosclerotic effects of secretory phospholipase A(2).