Lipoprotein-associated phospholipase A2 (platelet-activating factor acetylhydrolase) and cardiovascular disease

Abstract
Plasma lipoproteins carry a number of highly active enzymes in the circulation. One of these is lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet-activating factor acetylhydrolase. This review addresses the molecular properties of Lp-PLA2, the controversy surrounding its role in atherosclerosis and the regulation of its plasma levels in humans. Recent reports indicate that the enzyme Lp-PLA2 found in both LDL and HDL may be independently regulated in these lipoprotein subclasses and have distinct roles in atherogenesis. Seminal findings establishing the response-to-retention hypothesis of atherosclerosis support further the potentially damaging role that in-situ release of LDL-associated oxidative products by Lp-PLA2 may have in the formation of arterial wall lesions. In the mouse, where Lp-PLA2 circulates mainly bound to HDL, overexpression leads to reduced atherosclerosis, raising the possibility that the enzyme in HDL may have a protective role. Further evidence for a potential protective role is seen in studies of partial or complete deficiency of the enzyme. In the more general setting of population studies, however, it is clear that Lp-PLA2 is a positive risk factor for coronary disease and measurements of its mass may contribute to the prediction of coronary heart disease risk, especially in individuals with low LDL cholesterol levels. Lp-PLA2 is an enzyme with potentially multiple risks in atherosclerosis. In humans the weight of evidence suggests that it is a positive risk factor for coronary heart disease - an observation commensurate with its position in the direct pathological sequence leading from formation of oxidized LDL in the artery wall to cellular dysfunction and formation of lesions.

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