Biology of platelet-activating factor acetylhydrolase (PAF-AH, lipoprotein associated phospholipase A2)

Abstract

This article is focused on platelet-activating factor acetylhydrolase (PAF-AH), a lipoprotein bound, calcium-independent phospholipase A2 activity also referred to as lipoprotein-associated phospholipase A2 or PLA2G7. PAF-AH catalyzes the removal of the acyl group at the sn-2 position of PAF and truncated phospholipids generated in settings of inflammation and oxidant stress. Here, I discuss current knowledge related to the structural features of this enzyme, including the molecular basis for association with lipoproteins and susceptibility to oxidative inactivation. The circulating form of PAF-AH is constitutively active and its expression is upregulated by mediators of inflammation at the transcriptional level. This mechanism is likely responsible for the observed up-regulation of PAF-AH during atherosclerosis and suggests that increased expression of this enzyme is a physiological response to inflammatory stimuli. Administration of recombinant forms of PAF-AH attenuate inflammation in a variety of experimental models. Conversely, genetic deficiency of PAF-AH in defined human populations increases the severity of atherosclerosis and other syndromes. Recent advances pointing to an interplay among oxidized phospholipid substrates, Lp(a), and PAF-AH could hold the key to a number of unanswered questions. © 2008 Springer Science+Business Media, LLC.