Lipid surfaces of lipoproteins and oxidized phospholipids (OxPL)

Lipid surfaces of lipoproteins and oxidized phospholipids (OxPL) are critical damage-associated molecular patterns (DAMPs) that play a central role in the pathogenesis of chronic inflammatory and cardiovascular diseases. These targets are generated when polyunsaturated fatty acids within phospholipids undergo oxidative modification by reactive oxygen species, leading to the formation of reactive neo-epitopes on the surface of particles like oxidized low-density lipoprotein (OxLDL) and lipoprotein(a) [Lp(a)] (Tsimikas et al., 2018, J Lipid Res). These oxidized surfaces are recognized by the innate immune system through scavenger receptors such as CD36 and Toll-like receptors, which triggers macrophage activation, foam cell formation, and the secretion of pro-inflammatory cytokines (Binder et al., 2016, Nat Rev Cardiol). In clinical contexts, the accumulation of OxPL on lipoproteins is strongly associated with the progression of atherosclerosis and calcific aortic valve stenosis (Que et al., 2018, Nature). Therapeutic interventions aim to neutralize these pro-inflammatory lipids using specialized monoclonal antibodies, such as E06, or small molecules like VB-201 that inhibit the downstream signaling cascades initiated by OxPL (Witztum and Tsimikas, 2012, J Lipid Res). By specifically targeting these lipid modifications, researchers hope to address the residual inflammatory risk that remains in patients even after intensive cholesterol-lowering therapy.

Other names

Oxidized phospholipidsOxidized low-density lipoprotein surfacesOxLDL epitopesPro-inflammatory lipid epitopesPhospholipid oxidation products

Neutralization of pro-inflammatory epitopes, inhibition of scavenger receptor (e.g., CD36) binding, and modulation of Toll-like receptor (TLR) signaling pathways.