Inflammation
Oxidized phospholipids bind apo(a) via a specific kringle site unique to humans, explaining Lp(a) pro-atherogenic potential, a mechanistic study (J Lipid Res 2013)
Original title: Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a)
This study examined what determines oxidized phospholipid (OxPL) binding to apolipoprotein(a) [apo(a)] and Lp(a), testing plasma from humans, apes, monkeys, apo(a)/Lp(a) transgenic mice, lysine-binding-site mutant mice, and recombinant apo(a) constructs. Using antibody E06, which binds the phosphocholine headgroup of OxPLs, the researchers found E06-detectable OxPLs only in apo(a) with an intact kringle IV type 10 (KIV10) lysine-binding site, while mass spectrometry confirmed both E06- and non-E06-detectable OxPLs covalently bound to apo(a) fragments, some removable by saponification. PC-containing OxPLs were still present, but not E06-reactive, in a recombinant apo(a) construct with a KIV10 lysine-binding-site mutation. The findings show pro-inflammatory, immune-accessible OxPLs on Lp(a) are strongly influenced by the KIV10 lysine-binding site and unique to human apo(a), potentially explaining Lp(a) pro-atherogenic properties.
Original abstract
Oxidized phospholipids (OxPLs) are present on apolipoprotein (a) [apo(a)] and lipoprotein (a) [Lp(a)] but the determinants influencing their binding are not known. The presence of OxPLs on apo(a)/Lp(a) was evaluated in plasma from healthy humans, apes, monkeys, apo(a)/Lp(a) transgenic mice, lysine binding site (LBS) mutant apo(a)/Lp(a) mice with Asp(55/57)→Ala(55/57) substitution of kringle (K)IV10)], and a variety of recombinant apo(a) [r-apo(a)] constructs. Using antibody E06, which binds the phosphocholine (PC) headgroup of OxPLs, Western and ELISA formats revealed that OxPLs were only present in apo(a) with an intact KIV10 LBS. Lipid extracts of purified human Lp(a) contained both E06- and nonE06-detectable OxPLs by tandem liquid chromatography-mass spectrometry (LC-MS/MS). Trypsin digestion of 17K r-apo(a) showed PC-containing OxPLs covalently bound to apo(a) fragments by LC-MS/MS that could be saponified by ammonium hydroxide. Interestingly, PC-containing OxPLs were also present in 17K r-apo(a) with Asp(57)→Ala(57) substitution in KIV10 that lacked E06 immunoreactivity. In conclusion, E06- and nonE06-detectable OxPLs are present in the lipid phase of Lp(a) and covalently bound to apo(a). E06 immunoreactivity, reflecting pro-inflammatory OxPLs accessible to the immune system, is strongly influenced by KIV10 LBS and is unique to human apo(a), which may explain Lp(a)'s pro-atherogenic potential.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.