Platelet-activating factor acetylhydrolase (PAF-AH)

Platelet‐activating factor acetylhydrolase (PAF-AH) is an extracellular enzyme primarily found in plasma where it circulates bound to low-density and high-density lipoproteins. It specifically hydrolyzes the sn‐2 acetyl group from platelet‐activating factor—a potent pro-inflammatory phospholipid—thereby rendering it biologically inactive. This action serves as an important regulatory mechanism for controlling inflammation, vascular permeability, hypotension, platelet aggregation, asthma attacks, allergic reactions, and other immune responses triggered by excessive PAF signaling. The enzyme also degrades oxidatively truncated phospholipids generated during oxidative stress. Structurally classified within the serine hydrolases/phospholipases A₂ family with a classic α/β-hydrolase fold containing a catalytic triad at its active site,[1] plasma forms are sometimes referred to as "lipoprotein-associated phospholipase A₂" due to their tight association with circulating lipoproteins.[5] Genetic variants affecting intracellular isoforms can contribute to neurodevelopmental disorders.[3] Because elevated activity has been linked epidemiologically to increased cardiovascular risk—including stroke—therapeutic inhibition has been explored but remains clinically controversial due to mixed trial results regarding efficacy versus safety.[4][5]

Other names

Lipoprotein-associated phospholipase A2 (Lp-PLA2)Plasma PAF-acetylhydrolasePAFAHPlatelet activating factor acetylhydrolase 1b catalytic subunit 3 (for the gene/protein product PAFAH1B3)PAF acetylhydrolase

Drugs targeting this molecule typically act by inhibiting its enzymatic activity to reduce hydrolysis of pro-inflammatory lipids. For example, darapladib inhibits Lp‑PLA₂ to decrease production of lysophosphatidylcholine and oxidized nonesterified fatty acids implicated in vascular inflammation.