Identification of Oxidized Phosphatidylinositols Present in OxLDL and Human Atherosclerotic Plaque

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• 作者：Devin Hasanally ; Andrea Edel ; Rakesh Chaudhary ; Amir Ravandi
• 关键词：Oxidized phospholipids ; Lipoproteins ; OxLDL ; Mass spectrometry ; Phosphatidylinositol ; Atheroma ; Atherosclerosis
• 刊名：Lipids
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：52
• 期：1
• 页码：11-26
• 全文大小：
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Lipidology; Neurochemistry; Medical Biochemistry; Nutrition; Medicinal Chemistry; Microbial Genetics and Genomics;
• 出版者：Springer Berlin Heidelberg
• ISSN：1558-9307
• 卷排序：52

文摘

Oxidized low-density lipoprotein (OxLDL) plays an important role in initiation and progression of atherosclerosis. Proatherogenic effects of OxLDL have been attributed to bioactive phospholipids generated during LDL oxidation. It is unknown what effect oxidation has on the phosphatidylinositol (PtdIns) molecules in LDL, even though PtdIns is 6% of the total LDL phospholipid pool. We sought to identify and quantitate oxidized phosphatidylinositol (OxPtdIns) species in OxLDL and human atherosclerotic plaque. Bovine liver PtdIns was subjected to non-enzymatic and lipoxygenase-catalyzed oxidation. Reversed-phase liquid chromatography with negative ESI–MS identified and confirmed compounds by fragmentation pattern analysis from which an OxPtdIns library was generated. Twenty-three OxPtdIns molecules were identified in copper-oxidized human LDL at 0, 6, 12, 24, 30, and 48 h, and in human atherosclerotic plaque. In OxLDL, OxPtdIns species containing aldehydes and carboxylates comprised 17.3 ± 0.1 and 0.9 ± 0.2%, respectively, of total OxPtdIns in OxLDL at 48 h. Hydroperoxides and isoprostanes at 24 h (68.5 ± 0.2 and 22.8 ± 0.2%) were significantly greater than 12 h (P < 0.01) without additional changes thereafter. Hydroxides decreased with increased oxidation achieving a minimum at 24 h (5.2 ± 0.3%). Human atherosclerotic plaques contained OxPtdIns species including aldehydes, carboxylates, hydroxides, hydroperoxides and isoprostanes, comprising 18.6 ± 4.7, 1.5 ± 0.7, 16.5 ± 7.4, 33.3 ± 1.1 and 30.2 ± 3.3% of total OxPtdIns compounds. This is the first identification of OxPtdIns molecules in human OxLDL and atherosclerotic plaque. With these novel molecules identified we can now investigate their potential role in atherosclerosis.