Proudfoot Julie M, Barden Anne E, Croft Kevin D, Galano Jean-Marie, Durand Thierry, Bultel-Poncé Valérie, Giera Martin, Mori Trevor A
a School of Medicine and Pharmacology , University of Western Australia, Royal Perth Hospital Unit , Perth , Australia.
b Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, CNRS, Université de Montpellier, ENSCM , Montpellier , France.
Free Radic Res. 2016 Dec;50(12):1374-1385. doi: 10.1080/10715762.2016.1250262. Epub 2016 Nov 7.
Low HDL cholesterol (HDL-C) is a risk factor for coronary artery disease (CAD). However, interventions that raise HDL-C have failed to reduce cardiovascular events. We previously reported that HDL is the main carrier of plasma F-isoprostanes (F-IsoPs) that are markers of oxidative stress formed upon oxidation of arachidonic acid. F-IsoPs are predominantly associated with phospholipids. However, there is evidence that F-IsoPs in the liver of rats treated with carbon tetrachloride associate with the neutral lipids. To date it is not known whether F-IsoPs are found in the neutral lipids in HDL in humans. Possible candidate neutral lipids include cholesteryl esters, triglycerides, diglycerides, and monoglycerides. This study aimed to identify the lipid classes within native and oxidized HDL that contain F-IsoPs. We showed that F-IsoPs in HDL are bound to neutral lipids as well as phospholipids. HDL-3 contained the highest concentration of F-IsoPs in all lipid classes before and after in vitro oxidation. Using targeted LC/MS and high resolution MS, we were unable to provide conclusive evidence for the presence of the synthesized standards 15(R)-15-F-isoP cholesterol and 1-ent-15(RS)-15-F-isoprostanoyl-sn-glycerol in the neutral lipids of HDL. Our findings show that oxidized lipids such as F-IsoPs are found in the core and surface of HDL. However, the exact molecular species remain to be definitively characterized. Future studies are required to determine whether the presence of F-IsoPs in neutral lipids alters HDL function.
低高密度脂蛋白胆固醇（HDL-C）是冠状动脉疾病（CAD）的一个危险因素。然而，提高HDL-C的干预措施未能减少心血管事件。我们之前报道过，HDL是血浆F-异前列腺素（F-IsoPs）的主要载体，F-异前列腺素是花生四烯酸氧化后形成的氧化应激标志物。F-异前列腺素主要与磷脂相关。然而，有证据表明，用四氯化碳处理的大鼠肝脏中的F-异前列腺素与中性脂质相关。迄今为止，尚不清楚人类HDL中的中性脂质中是否存在F-异前列腺素。可能的候选中性脂质包括胆固醇酯、甘油三酯、甘油二酯和甘油单酯。本研究旨在确定天然和氧化HDL中含有F-异前列腺素的脂质类别。我们发现，HDL中的F-异前列腺素与中性脂质以及磷脂结合。在体外氧化前后，HDL-3在所有脂质类别中F-异前列腺素的浓度最高。使用靶向液相色谱/质谱联用仪和高分辨率质谱，我们无法为HDL中性脂质中合成标准品15(R)-15-F-异前列腺素胆固醇和1-对映体-15(RS)-15-F-异前列腺素基-sn-甘油的存在提供确凿证据。我们的研究结果表明，氧化脂质如F-异前列腺素存在于HDL的核心和表面。然而，确切的分子种类仍有待明确表征。需要进一步的研究来确定中性脂质中F-异前列腺素的存在是否会改变HDL的功能。
