Lipoprotein-associated phospholipase A2 (platelet-activating factor acetylhydrolase) and cardiovascular disease
- 1 August 2003
- journal article
- review article
- Published by Wolters Kluwer Health in Current Opinion in Lipidology
- Vol. 14 (4), 347-352
- https://doi.org/10.1097/00041433-200308000-00002
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.Keywords
This publication has 47 references indexed in Scilit:
- New to Journal of Lipid ResearchJournal of Lipid Research, 2002
- Lipoprotein-associated phospholipase A2: a target directed at the atherosclerotic plaqueEmerging Therapeutic Targets, 2002
- Study of the paraoxonase and platelet-activating factor acetylhydrolase activities with agingProstaglandins, Leukotrienes & Essential Fatty Acids, 2001
- Anti-atherosclerotic effect of SB-244323, a lipoprotein associated phospholipase A2 inhibitor, in WHHL rabbitsAtherosclerosis, 2000
- Oxidized phospholipids activate PPARα in a phospholipase A2‐dependent mannerFEBS Letters, 2000
- Lipoprotein-Associated Phospholipase A 2 , Platelet-Activating Factor Acetylhydrolase, Is Expressed by Macrophages in Human and Rabbit Atherosclerotic LesionsArteriosclerosis, Thrombosis, and Vascular Biology, 1999
- Cellular Source(s) of Platelet-Activating-Factor Acetylhydrolase Activity in PlasmaBiochemical and Biophysical Research Communications, 1999
- Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitorBiochemical Journal, 1999
- A Mutation in Plasma Platelet-Activating Factor Acetylhydrolase (Val 279 →Phe) is a Genetic Risk Factor for StrokeStroke, 1997
- Distribution of PAF-acetylhydrolase activity in human plasma low-density lipoprotein subfractionsBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1994