Oxidized phospholipids on lipoprotein surfaces (OxPL)

Oxidized phospholipids (OxPL) and oxidized fatty acids are bioactive lipid species formed through the enzymatic or non-enzymatic oxidation of polyunsaturated fatty acids on the surface of lipoproteins, most notably Lipoprotein(a) [Lp(a)] and Low-Density Lipoprotein (LDL) (Source 1.1.1, 1.4.1). These molecules function as oxidation-specific epitopes (OSEs) and damage-associated molecular patterns (DAMPs) that are recognized by the innate immune system via scavenger receptors like CD36 and natural antibodies such as E06 (Source 1.3.2, 1.3.4). In the vascular wall, OxPL promote pro-inflammatory signaling, monocyte recruitment, and the transformation of macrophages into foam cells, which are foundational steps in the development of atherosclerosis (Source 1.3.1, 1.3.3). Furthermore, OxPL are strongly implicated in the progression of calcific aortic valve stenosis by stimulating valvular interstitial cell calcification and chronic inflammation (Source 1.4.2, 1.4.3). Therapeutic targeting of these lipids primarily involves reducing the plasma concentration of their main carrier, Lp(a), using antisense oligonucleotides like pelacarsen or siRNA like olpasiran, as well as experimental approaches using monoclonal antibodies or mimetic peptides to neutralize the epitopes directly (Source 1.2.1, 1.5.3).

Other names

Oxidized phospholipidsOxPL-apoBOxPL-apo(a)Oxidation-specific epitopesOSEsOxidized fatty acidsOxFFAOxidized low-density lipoprotein epitopes

Reduction of Lipoprotein(a) plasma levels through inhibition of apolipoprotein(a) synthesis, neutralization of oxidation-specific epitopes by monoclonal antibodies, and sequestration of oxidized lipids by apolipoprotein A-I mimetics.