RECENT FINDINGS: Recent reports have linked
Lp-PLA2 enrichment not only to the most atherogenic of
LDL particles but also to the most advanced,
rupture-prone, plaques. Electronegative
LDL has been shown to be highly enriched in
Lp-PLA2; and in advanced
atheroma,
Lp-PLA2 levels are highly upregulated, colocalizing with macrophages in both the necrotic core and fibrous cap.
Lp-PLA2 is well placed, whether on an oxidation susceptible
LDL particle or in the highly oxidative environment of an advanced
rupture-prone plaque, to hydrolyse oxidized
phospholipid and generate significant quantities of the two pro-inflammatory mediators,
lysophosphatidylcholine and oxidized nonesterified
fatty acid. Several studies have confirmed that
Lp-PLA2 is an independent risk factor for cardiovascular events (i.e.
myocardial infarction and
stroke). Although epidemiology studies consistently support a relationship between plasma
Lp-PLA2 levels and susceptibility to
coronary heart disease this is not the case for
Lp-PLA2 polymorphisms. Two clinical studies have linked the Ala-379-->Val polymorphism with a reduced risk of
myocardial infarction, but functional differences between the AA and VV polymorphs have yet to be demonstrated.
SUMMARY:
Lp-PLA2 is intimately associated with several aspects of human
atherogenesis. Although various
lipid-lowering
therapies, such as
statins, have been shown to reduce plasma levels of
Lp-PLA2, none has been studied in terms of its ability to lower the large macrophage-mediated upregulation of
Lp-PLA2 within advanced plaques.