Phosphocholine headgroup of oxidized phosphatidylcholine (PC-OxPC)

The phosphocholine (PC) headgroup of oxidized phosphatidylcholine (OxPC) is a prominent oxidation-specific epitope (OSE) and a well-characterized damage-associated molecular pattern (DAMP) (1.3.1, 3.1.2). In healthy cells, the PC headgroup of phosphatidylcholine is typically sequestered or oriented in a way that it is not recognized by the innate immune system; however, upon oxidative stress, the polyunsaturated fatty acid at the sn-2 position undergoes peroxidation and fragmentation, leading to a conformational change that exposes the PC headgroup (1.3.1, 4.2.2). This exposed PC moiety is found on oxidized low-density lipoprotein (OxLDL) and the membranes of apoptotic or damaged cells, where it is recognized by innate immune components such as C-reactive protein (CRP), scavenger receptors like CD36, and natural IgM antibodies like the EO6/T15 idiotype (1.3.2, 2.4.2, 3.1.5). Therapeutically, targeting the PC headgroup of OxPC aims to neutralize the pro-inflammatory and pro-atherogenic effects of oxidized phospholipids (1.4.3, 2.3.3). Monoclonal antibodies like EO6 and its humanized derivatives have been shown to block the uptake of OxLDL by macrophages, thereby preventing foam cell formation and the progression of atherosclerosis (2.3.3, 2.4.4). Additionally, small molecule analogs like VB-201 (lecinoxoids) compete with oxidized phospholipids for binding to receptors like TLR2 and CD14, modulating the inflammatory response in conditions such as cardiovascular disease, nonalcoholic steatohepatitis (NASH), and neurodegenerative disorders (2.2.1, 2.2.2, 2.5.3).

Other names

Phosphorylcholine headgroup of oxidized phospholipidsOxPC epitopePC-OxPLOxidation-specific epitopeOSEPC-DAMP

Neutralization of pro-inflammatory oxidized phospholipids, inhibition of scavenger receptor (CD36) binding, inhibition of TLR2/TLR4 signaling, and promotion of apoptotic cell clearance.