title: Protective role of heme oxygenase-1 against inflammation in atherosclerosis.
abstract: Heme oxygenase-1 (HO-1) catalyzes the first and rate-limiting step in the metabolism of free heme into equimolar amounts of ferrous iron, carbon monoxide (CO), and biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. HO-1 has recently been identified as a promising therapeutic target in the treatment of vascular inflammatory disease, including atherosclerosis. HO-1 represses inflammation by removing the pro-inflammatory molecule heme and by generating CO and the bile pigments, biliverdin and bilirubin. These HO-1 reaction products are capable of blocking innate and adaptive immune responses by modifying the activation, differentiation, maturation, and/or polarization of numerous immune cells, including endothelial cells, monocytes/macrophages, dendritic cells, T lymphocytes, mast cells, and platelets. These cellular actions by CO and bile pigments result in diminished leukocyte recruitment and infiltration, and pro-inflammatory mediator production within atherosclerotic lesions. This review highlights the mechanisms by which HO-1 suppresses vascular inflammation in atherosclerosis, and explores possible therapeutic modalities by which HO-1 and its reaction products can be employed to ameliorate vascular inflammatory disease.
authors.affiliation: Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO, USA. durantew@health.missouri.edu
authors.forename: William
authors.initials: W
authors.lastname: Durante
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D006418:Heme; D051547:Heme Oxygenase-1