Oxidative Phospholipidomics in health and disease: Achievements, challenges and hopes

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Phospholipid peroxidation products are recognized as important bioactive lipid mediators playing an active role as modulators in signalling events in inflammation, immunity and infection. The biochemical responses are determined by the oxidation structural features present in oxPL modulating biophysical and biological properties in model membranes and lipoproteins. In spite of the extensive work conducted with model systems over the last 20 years, the study of oxPL in biological systems has virtually stagnated. In fact, very little is known concerning the predominant oxPL in fluids and tissues, their basal levels, and any variations introduced with age, gender and ethnicity in health and disease. In consequence, knowledge on oxPL has not yet translated into clinical diagnostic, in the early and timely diagnosis of “silent” diseases such as atherosclerosis and cardiovascular diseases, or as prognosis tools in disease stratification and particularly useful in the context of multimorbidities. Their use as therapeutic solutions or the development of innovative functional biomaterials remains to be explored.This review summarizes the achievements made in the identification of oxPL revealing an enormous structural diversity. A brief overview of the challenges associated with the analysis of such diverse array of products is given and a critical evaluation on key aspects in the analysis pipeline that need to be addressed. Once these issues are addressed, Oxidative Phospholipidomics will hopefully lead to major breakthrough discoveries in biochemistry, pharmaceutical, and clinical areas for the upcoming 20 years. This article is part of Special Issue entitled 4-Hydroxynonenal and Related Lipid Oxidation Products.HighlightsOxidative studies in model membranes show a wide diversity of oxPL.Panel of oxPL found in fluids and cells is small.Levels of oxPL with age, gender and ethnicity in health and disease remain elusive.Low oxPL/PL ex vivo poses analytical and instrumental challenges to oxPL detection.OxPL affects the organization of membranes though distribution is unknown.Insight on predominant oxPL structural motifs is key to unravel LDL atherogenicity.Routine oxPL analysis and integration of omic platforms will move the field forward.

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