Pathophysiological Role and Clinical Significance of Lipoprotein-Associated Phospholipase A₂ (Lp-PLA₂) Bound to LDL and HDL

Title:Pathophysiological Role and Clinical Significance of Lipoprotein-Associated Phospholipase A₂ (Lp-PLA₂) Bound to LDL and HDL

Volume: 20 Issue: 40

Author(s): Constantinos C. Tellis and Alexandros D. Tselepis

Affiliation:

Keywords: Atherosclerosis, Cardiovascular disease, Darapladib, Lipoproteins, LDL, HDL, Lp-PLA₂.

Abstract: 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.

Cite this article as:

Tellis C. Constantinos and Tselepis D. Alexandros, Pathophysiological Role and Clinical Significance of Lipoprotein-Associated Phospholipase A₂ (Lp-PLA₂) Bound to LDL and HDL, Current Pharmaceutical Design 2014; 20 (40) . https://dx.doi.org/10.2174/1381612820666140622200916