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Biology of Platelet-activating Factor Acetylhydrolase (PAF-AH, Lipoprotein Associated Phospholipase A2)

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Abstract

Introduction

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.

Discussion

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.

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Acknowledgments

This work was supported by National Institutes of Health grant HL35828 and by the Huntsman Cancer Foundation. I am indebted to many students, trainees, technicians, and post-doctoral fellows for their contributions over the years. I also wish to express my gratitude to multiple long-time colleagues and collaborators.

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  1. Huntsman Cancer Institute and Department of Internal Medicine, University of Utah, 2000 Circle of Hope, Suite 3364, Salt Lake City, UT, 84112-5550, USA

    Diana M. Stafforini

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Stafforini, D.M. Biology of Platelet-activating Factor Acetylhydrolase (PAF-AH, Lipoprotein Associated Phospholipase A2). Cardiovasc Drugs Ther 23, 73–83 (2009). https://doi.org/10.1007/s10557-008-6133-8

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  • DOI: https://doi.org/10.1007/s10557-008-6133-8

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