Exploring the Biomedical Significance of Oxidized Phospholipids as Biomarkers, Drug Targets and Drug Leads Across Multiple Diseases

Abstract

Enzymatic oxidation or autooxidation of esterified polyunsaturated fatty acids (PUFA) residues within phospholipids in cell membranes or circulating lipoprotein particles leads to the formation of a broad range of oxidized phospholipid (OxPL) species. During the last two decades, OxPLs have been extensively characterized as drivers of pathology in multiple inflammatory and metabolic conditions. Chronically elevated OxPL levels present in tissues, circulation, and atherosclerotic plaques are thought to induce or accompany pro-inflammatory and injurious effects on blood-, vessel wall cells as well as cells in different organs, which can lead to the development or worsening of metabolic, cardiovascular diseases, age-associated brain diseases, allergy, asthma, cancer or inflammatory pain. Analysis of the structure-activity relationship however identified specific OxPL products exhibiting prominent anti-inflammatory, pro-survival, and endothelial barrier protective properties. This study reviewed and briefly summarized the rapidly accumulating evidence pointing to the importance of OxPLs in pathology where they can play multiple roles of biomarkers, drug targets, and drug leads.