Lipoprotein-associated phospholipase A2 (platelet-activating factor acetylhydrolase) and cardiovascular disease.
OBJECTIVE
Plasma lipoproteins carry a number of highly active enzymes in the circulation. One of these is lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), also known as platelet-activating factor acetylhydrolase. This review addresses the molecular properties of Lp-PLA(2), the controversy surrounding its role in atherosclerosis and the regulation of its plasma levels in humans.


RESULTS
Recent reports indicate that the enzyme Lp-PLA(2) 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-PLA(2) may have in the formation of arterial wall lesions. In the mouse, where Lp-PLA(2) 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-PLA(2) 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.


CONCLUSIONS
Lp-PLA(2) 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.
Caslake
Muriel J
MJ
Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, UK. m.caslake@clinmed.gla.ac.uk
Packard
Chris J
CJ
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000209:etiology; D016022:Case-Control Studies; D002986:Clinical Trials as Topic; D006801:Humans; D010741:Phospholipases A / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054467:Phospholipases A2; D015539:Platelet Activation; D012307:Risk Factors
D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase