title: Biological and pathophysiological roles of end-products of DHA oxidation.
abstract: Polyunsaturated fatty acids (PUFA) are known to be present and/or enriched in vegetable and fish oils. Among fatty acids, n-3 PUFA are generally considered to be protective in inflammation-related diseases. The guidelines for substituting saturated fatty acids for PUFAs have been highly publicized for decades by numerous health organizations. Recently, however, the beneficial properties of n-3 PUFA are questioned by detailed analyses of multiple randomized controlled clinical trials. The reported heterogeneity of results is likely due not only to differential effects of PUFAs on various pathological processes in humans, but also to the wide spectrum of PUFA's derived products generated in vivo.
  
  
  
  The goal of this review is to discuss the studies focused on well-defined end-products of PUFAs oxidation, their generation, presence in various pathological and physiological conditions, their biological activities and known receptors. Carboxyethylpyrrole (CEP), a DHA-derived oxidized product, is especially emphasized due to recent data demonstrating its pathophysiological significance in many inflammation-associated diseases, including atherosclerosis, hyperlipidemia, thrombosis, macular degeneration, and tumor progression.
  
  
  
  CEP is a product of radical-based oxidation of PUFA that forms adducts with proteins and lipids in blood and tissues, generating new powerful ligands for TLRs and scavenger receptors. The interaction of CEP with these receptors affects inflammatory response, angiogenesis, and wound healing.
  
  
  
  The detailed understanding of CEP-mediated cellular responses may provide a basis for the development of novel therapeutic strategies and dietary recommendations.
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States; Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
authors.forename: Valentin P
authors.initials: VP
authors.lastname: Yakubenko
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States. Electronic address: byzovat@ccf.org.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Byzova
mesh_terms: D000818:Animals; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005395:Fish Oils / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D010084:Oxidation-Reduction; D016032:Randomized Controlled Trials as Topic
chemical_list: D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils
keywords: CD36; Carboxyethylpyrrole; Docosahexaenoic acid; Inflammation; Polyunsaturated fatty acids; Toll-like receptors