Oxidized phospholipids structurally related to platelet-activating factor (OxPLs-PAF)

Oxidized phospholipids (OxPLs) structurally related to platelet-activating factor (PAF) are a class of bioactive lipids generated through the non-enzymatic oxidation of polyunsaturated fatty acids in phospholipids, such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) (Podrez et al., 1999, J. Biol. Chem.). These molecules, including 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC), possess a shortened sn-2 side chain that allows them to mimic the structure of PAF and bind to the platelet-activating factor receptor (PAFR) (Leitinger, 2003, Curr. Opin. Lipidol.). Beyond PAFR, they interact with scavenger receptors like CD36 and Toll-like receptors (TLR2 and TLR4), triggering potent pro-inflammatory and pro-thrombotic signaling pathways (Zhu et al., 2012, J. Exp. Med.). In diseases like atherosclerosis and chronic inflammation, the accumulation of these OxPLs in cell membranes and lipoproteins drives endothelial dysfunction and leukocyte recruitment (Que et al., 2018, Nature). Therapeutic strategies involve the use of synthetic analogs like VB-201 (Lecinoxoid) to modulate their signaling or monoclonal antibodies like E06 to neutralize their activity (VBL Therapeutics; Tsimikas et al., 2010, J. Am. Coll. Cardiol.).

Other names

PAF-like oxidized phospholipidsOxidized phospholipidsOxPLsPAF-like lipidsPOVPCPGPCOxPAPC derivatives

Competitive inhibition of the platelet-activating factor receptor (PAFR), modulation of TLR2/CD36 signaling complexes, and neutralization of pro-inflammatory lipid species.