Lipoprotein-associated phospholipase A2 (Lp-PLA2), also named as platelet-activating factor (PAF)-acetylhydrolase, exhibits a
Ca2+-independent phospholipase A2 activity and catalyzes the hydrolysis of the ester bond at the sn-2 position of PAF and oxidized phospholipids
(oxPL). These phospholipids are formed under oxidative and inflammatory conditions, and may play important roles in atherogenesis.
The vast majority of plasma Lp-PLA2 mass binds to low-density lipoprotein (LDL) while a smaller amount is associated with
high-density lipoprotein (HDL). Lp-PLA2 is also bound to lipoprotein (a) [Lp(a)], very low-density lipoprotein (VLDL) and remnant
lipoproteins. Several lines of evidence suggest that the role of plasma Lp-PLA2 in atherosclerosis may depend on the type of lipoprotein
particle with which this enzyme is associated. Data from large Caucasian population studies have supported plasma Lp-PLA2 (primarily
LDL-associated Lp-PLA2) as a cardiovascular risk marker independent of, and additive to, traditional risk factors. On the contrary, the
HDL-associated Lp-PLA2 may express antiatherogenic activities and is also independently associated with lower risk for cardiac death.
The present review presents data on the biochemical and enzymatic properties of Lp-PLA2 as well as its structural characteristics that determine
the association with LDL and HDL. We also critically discuss the possible pathophysiological and clinical significance of the Lp-
PLA2 distribution between LDL and HDL in human plasma, in view of the results of prospective epidemiologic studies on the association
of Lp-PLA2 with future cardiovascular events as well the recent studies that evaluate the possible effectiveness of specific Lp-PLA2 inhibitors
in reducing residual cardiovascular risk.
Keywords: Atherosclerosis, Cardiovascular disease, Darapladib, Lipoproteins, LDL, HDL, Lp-PLA2.
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