Platelet-activating factor acetylhydrolase (PLA2G7) (Lp-PLA2)

Platelet-activating factor acetylhydrolase (PAF-AH), specifically the secreted isoform known as lipoprotein-associated phospholipase A2 (Lp-PLA2), is a calcium-independent enzyme primarily synthesized and secreted by leukocytes, including macrophages, monocytes, and lymphocytes [1][2]. Its primary biological function is the hydrolysis of platelet-activating factor (PAF), a potent phospholipid mediator of inflammation, into the inactive metabolite lyso-PAF [1]. Beyond its role with PAF, Lp-PLA2 also hydrolyzes oxidized phospholipids within low-density lipoprotein (LDL) particles, releasing pro-inflammatory products such as lysophosphatidylcholine (lyso-PC) and oxidized fatty acids [2][4]. These products are known to promote leukocyte chemotaxis and contribute to the progression and instability of atherosclerotic plaques [2]. Consequently, Lp-PLA2 has been identified as a therapeutic target for reducing vascular inflammation and preventing cardiovascular events [3]. While small-molecule inhibitors like darapladib were developed to target this enzyme, they have faced significant challenges in clinical trials, failing to show a substantial reduction in major adverse cardiovascular events despite potent enzyme inhibition [3][5].

Other names

Lipoprotein-associated phospholipase A2Lp-PLA2Group VII phospholipase A2PAF-AHLDL-associated phospholipase A2Phospholipase A2 group VII

Reversible inhibition of the phospholipase A2 activity of the enzyme, preventing the hydrolysis of oxidized phospholipids and the subsequent release of pro-inflammatory mediators like lysophosphatidylcholine.