Secretory phospholipase A₂ in atherogenesis

Purpose of review: Immunohistochemistry studies have confirmed the presence of group IIA, group V and group X secretory phospholipase A₂ in human or mouse atherosclerotic lesions. The possibility that secretory phospholipase A₂ 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 A₂ 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 A₂ 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 A₂ 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 A₂ hydrolysis generates pro-atherogenic LDL. These data, coupled with the finding that macrophage-specific expression of human group IIA secretory phospholipase A₂ 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 A₂ 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 A₂.