Secretory phospholipase A2 enzymes in atherogenesis.
OBJECTIVE
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.


RESULTS
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 A2 as an attractive target for the treatment of atherosclerotic disease.


CONCLUSIONS
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.
Webb
Nancy R
NR
Department of Internal Medicine, University of Kentucky, Lexington, Kentucky 40536-0200, USA. nrwebb1@uky.edu
D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D001161:Arteriosclerosis / Q000503:physiopathology*; D004195:Disease Models, Animal; D054501:Group II Phospholipases A2; D006801:Humans; D006868:Hydrolysis; D008074:Lipoproteins / Q000378:metabolism; D051379:Mice; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2
D008074:Lipoproteins; D016718:Arachidonic Acid; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2