Transfer and Enzyme-Mediated Metabolism of Oxidized Phosphatidylcholine and Lysophosphatidylcholine between Low- and High-Density Lipoproteins

• Main Authors: Naoko Sawada, Takashi Obama, Mirei Mizuno, Kiyoshi Fukuhara, Sanju Iwamoto, Toshihiro Aiuchi, Tomohiko Makiyama, Hiroyuki Itabe
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Antioxidants
• Subjects: oxidized phosphatidylcholine; lysophosphatidylcholine; HDL; oxLDL; Lp-PLA₂; LCAT
• Online Access: https://www.mdpi.com/2076-3921/9/11/1045

Oxidized low-density lipoprotein (oxLDL) and oxidized high-density lipoprotein (oxHDL), known as risk factors for cardiovascular disease, have been observed in plasma and atheromatous plaques. In a previous study, the content of oxidized phosphatidylcholine (oxPC) and lysophosphatidylcholine (lysoPC) species stayed constant in isolated in vivo oxLDL but increased in copper-induced oxLDL in vitro. In this study, we prepared synthetic deuterium-labeled 1-palmitoyl lysoPC and palmitoyl-glutaroyl PC (PGPC), a short chain-oxPC to elucidate the metabolic fate of oxPC and lysoPC in oxLDL in the presence of HDL. When LDL preloaded with d₁₃-lysoPC was mixed with HDL, d₁₃-lysoPC was recovered in both the LDL and HDL fractions equally. d₁₃-LysoPC decreased by 50% after 4 h of incubation, while d₁₃-PC increased in both fractions. Diacyl-PC production was abolished by an inhibitor of lecithin-cholesterol acyltransferase (LCAT). When d₁₃-PGPC-preloaded LDL was incubated with HDL, d₁₃-PGPC was transferred to HDL in a dose-dependent manner when both LCAT and lipoprotein-associated phospholipase A₂ (Lp-PLA₂) were inhibited. Lp-PLA₂ in both HDL and LDL was responsible for the hydrolysis of d₁₃-PGPC. These results suggest that short chain-oxPC and lysoPC can transfer between lipoproteins quickly and can be enzymatically converted from oxPC to lysoPC and from lysoPC to diacyl-PC in the presence of HDL.