Platelet-activating factor acetylhydrolase (PAF-AH) (PAF-AH)

Platelet-activating factor acetylhydrolase (PAF-AH), also known as lipoprotein-associated phospholipase A2 (Lp-PLA2), is a calcium-independent enzyme primarily produced by leukocytes such as macrophages and monocytes (Source: UniProt P78380). Its primary biological function is the hydrolysis of platelet-activating factor (PAF), a potent phospholipid mediator of inflammation, and the degradation of oxidized phospholipids (Source: PubMed PMID: 15132997). While the enzyme is synthesized within leukocytes, it is largely secreted into the circulation where it associates with low-density lipoprotein (LDL) particles (Source: NCBI Gene PLA2G7). In the context of disease, elevated levels of this enzyme are strongly associated with the progression of atherosclerosis and increased risk of cardiovascular events, as its activity generates pro-inflammatory products like lysophosphatidylcholine (Source: PubMed PMID: 24740124). Conversely, deficiency or low activity of PAF-AH in leukocytes has been linked to increased susceptibility to inflammatory conditions such as asthma and anaphylaxis (Source: PubMed PMID: 3065432). Therapeutic efforts have focused on small-molecule inhibitors like darapladib to reduce vascular inflammation, though these have struggled to demonstrate clinical efficacy in large-scale trials (Source: PubMed PMID: 24678979).

Other names

Lipoprotein-associated phospholipase A2Lp-PLA2Phospholipase A2 group VIIPLA2G71-alkyl-2-acetylglycerophosphocholine esterase

Inhibition of the enzymatic hydrolysis of oxidized phospholipids to prevent the formation of pro-inflammatory mediators like lysophosphatidylcholine.