title: Nitro-fatty acids in cardiovascular regulation and diseases: characteristics and molecular mechanisms.
abstract: Electrophilic nitro-fatty acids (NO2-FAs) are endogenously formed by redox reactions of nitric oxide ((.)NO)- and nitrite ((.)NO2)- derived nitrogen dioxide with unsaturated fatty acids. Nitration preferentially occurs on polyunsaturated fatty acids with conjugated dienes under physiological or pathophysiological conditions such as during digestion, metabolism and as adaptive inflammatory processes. Nitro-fatty acids are present in free and esterified forms achieving broad biodistribution in humans and experimental models. Structural, functional and biological characterization of NO2-FAs has revealed clinically relevant protection from inflammatory injury in a number of cardiovascular, renal and metabolic experimental models. NO2-FAs are engaged in posttranslational modifications (PTMs) of a selective redox sensitive pool of proteins and regulate key adaptive signaling pathways involved in cellular homeostasis and inflammatory response. Here, we review and update the biosynthesis, metabolism and signaling actions of NO2-FAs, highlighting their diverse protective roles relevant to the cardiovascular system.
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, University of Michigan, North Campus Research Complex 26, 2800 Plymouth Road, Ann Arbor, MI 48109,, luisvill@umich.edu.
authors.forename: Luis
authors.initials: L
authors.lastname: Villacorta
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, University of Michigan, North Campus Research Complex 26, 2800 Plymouth Road, Ann Arbor, MI 48109.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, E1343 Thomas E. Starzl Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Schopfer
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, E1343 Thomas E. Starzl Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Freeman
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, University of Michigan, North Campus Research Complex 26, 2800 Plymouth Road, Ann Arbor, MI 48109.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology; D005227:Fatty Acids / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology; D008171:Lung Diseases / Q000503:physiopathology; D008659:Metabolic Diseases / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology; D009569:Nitric Oxide / Q000737:chemistry*; D014657:Vasculitis / Q000503:physiopathology
chemical_list: D005227:Fatty Acids; D009569:Nitric Oxide