Electrophilic nitro-fatty acids: anti-inflammatory mediators in the vascular compartment.
Vascular inflammatory disorders are often associated with both decreased NO bioavailability and a lack of responsiveness to NO, a consequence of impaired NO biosynthesis, dysregulated l-arginine metabolism, endothelial nitric oxide synthase (eNOS) uncoupling and NO consumption induced by redox reactions of NO. The latter is mediated via oxidative inflammatory conditions altering NO-dependent endothelial function, including vascular tone and cell proliferation. The redox reactions of NO and byproducts such as nitrite can react to yield electrophilic nitro-fatty acid derivatives (NO(2)-FAs) and exemplify a biochemical convergence of reactions participating in NO and lipid signaling. NO(2)-FAs represent a novel therapeutic strategy to treat vascular disorders by improving endothelial dysfunction through enhancing NO signaling and blocking vascular smooth muscle proliferation, inflammation, and maladaptive remodeling.
Khoo
Nicholas K H
NK
Department of Pharmacology and Chemical Biology, E1314 BST, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. nkhoo@pitt.edu
Freeman
Bruce A
BA
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009574:Nitro Compounds / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists
D005227:Fatty Acids; D051267:NF-E2-Related Factor 2; D009574:Nitro Compounds; D047492:Peroxisome Proliferator-Activated Receptors; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D051547:Heme Oxygenase-1