Oxidized phospholipid and oxidized fatty acid (OxPL) (OxPL)

Oxidized phospholipids (OxPL) and oxidized fatty acids are bioactive lipid species generated through the oxidative modification of polyunsaturated fatty acids on the surface of low-density lipoproteins (LDL) and high-density lipoproteins (HDL). These molecules act as potent pro-inflammatory mediators and are recognized as danger-associated molecular patterns (DAMPs) by the innate immune system, specifically through scavenger receptors like CD36 and Toll-like receptors (TLR2/4) (Witztum & Lichtman, Nature, 2008). In the circulation, OxPL is predominantly covalently bound to Lipoprotein(a) [Lp(a)], making it a critical driver of atherosclerosis, calcific aortic valve stenosis, and systemic inflammation (Tsimikas et al., Nature Reviews Cardiology, 2018). Therapeutic strategies include the use of monoclonal antibodies like E06, which mimics natural IgM to neutralize the phosphocholine headgroup of OxPL, and the development of antisense oligonucleotides like pelacarsen that reduce the levels of the Lp(a) carrier (Que et al., Nature, 2018; Tsimikas et al., NEJM, 2020). By neutralizing or reducing these oxidized species, clinicians aim to decrease vascular wall inflammation and prevent the progression of chronic fibro-calcific diseases (Yeang et al., Chem Phys Lipids, 2016). These targets represent a novel frontier in addressing residual inflammatory risk in patients already receiving standard lipid-lowering therapies.

Other names

Oxidized LDLOxidized HDLOxidized lipidsOxPL-apoBOxPL-apoA1Bioactive oxidized phospholipids

Neutralization of pro-inflammatory phosphocholine headgroups on oxidized phospholipids or reduction of the lipoprotein(a) carrier to prevent activation of innate immune pathways.