Oxidized phospholipid (OxPL) (OxPL)

Oxidized phospholipids (OxPL) are bioactive lipid molecules generated through the oxidative modification of polyunsaturated fatty acids within phospholipids (Witztum & Tsimikas, 2012, J Lipid Res). They are predominantly found on the surface of pro-atherogenic lipoproteins, such as Lipoprotein(a) [Lp(a)] and oxidized low-density lipoprotein (oxLDL), as well as on the membranes of apoptotic cells and microvesicles (Tsimikas et al., 2005, NEJM). OxPL function as damage-associated molecular patterns (DAMPs) that trigger robust pro-inflammatory and pro-thrombotic responses by binding to scavenger receptors (e.g., CD36) and Toll-like receptors on macrophages and endothelial cells (Que et al., 2023, Nature Reviews Cardiology). In clinical contexts, OxPL are recognized as key drivers of atherosclerosis and calcific aortic valve stenosis, with the OxPL-apoB assay serving as a potent biomarker for cardiovascular risk (Capoulade et al., 2015, JACC). Therapeutic strategies focus on either directly neutralizing OxPL using monoclonal antibodies like E06 or indirectly reducing their levels by lowering the concentration of their primary carrier, Lp(a), using antisense oligonucleotides like pelacarsen or siRNA therapies like olpasiran (Tsimikas et al., 2020, NEJM).

Other names

Oxidized lipidsOxPL-apoBOxidized low-density lipoprotein-associated phospholipidsOxidized cell membrane lipidsOx-LDL associated phospholipids

Neutralization of pro-inflammatory lipid species or reduction of lipoprotein carriers such as Lipoprotein(a) to decrease systemic OxPL burden.