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

• Published in: Antioxidants Vol. 9; no. 11; p. 1045
• Main Authors: Sawada, Naoko, Obama, Takashi, Mizuno, Mirei, Fukuhara, Kiyoshi, Iwamoto, Sanju, Aiuchi, Toshihiro, Makiyama, Tomohiko, Itabe, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 26.10.2020; MDPI
• Subjects: Acyltransferase; Blood lipoproteins; Cardiovascular diseases; Charged particles; Cholesterol; Chromatography; Enzymes; HDL; Health aspects; High density lipoprotein; LCAT; Lecithin; Lipids; Lipoproteins; Low density lipoprotein; Lp-PLA2; Lysophosphatidylcholine; Mass spectrometry; Metabolism; Observations; Oxidation; oxidized phosphatidylcholine; oxLDL; Phosphatidylcholine; Phospholipase A2; Plaques; Plasma; Proteins; Proteolipids; Risk factors; Scientific imaging; Japan; United States > US
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox9111045

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.