title: Niacin inhibits vascular inflammation via the induction of heme oxygenase-1.
abstract: BACKGROUND
  Heme oxygenase-1 (HO-1) is a cytoprotective protein whose expression is consistently associated with therapeutic benefits in a number of pathological conditions such as atherosclerotic vascular disease and inflammation. Niacin is a pleiotropic drug that slows the progression of coronary artery disease and increases serum levels of the HO-1 enzymatic product bilirubin. This study asks if the cardioprotective properties of niacin involve the induction of HO-1.
  
  
  RESULTS
  New Zealand White rabbits received chow or chow supplemented with 0.6% (wt/wt) niacin for 2 weeks. Acute vascular inflammation was induced in the animals by placing a nonocclusive silastic collar around the left common carotid artery. At 24 hours after collar implantation, serum bilirubin and vascular, liver, and spleen HO-1 messenger RNA levels were significantly increased. Vascular inflammation was decreased in the niacin-supplemented animals compared with control. Treatment of the animals with tin protoporphyrin-IX, a global HO inhibitor, or HO-1 small interfering RNA to knock down carotid artery HO-1 attenuated the ability of niacin to inhibit vascular inflammation. Treatment of cultured human coronary artery endothelial cells with niacin increased HO-1 expression by activating the nuclear factor-E2-related factor 2/p38 mitogen-activated protein kinase signaling pathway and inhibiting tumor necrosis factor α-induced endothelial inflammation. The antiinflammatory effects of niacin in human coronary artery endothelial cells were mimicked by bilirubin and abolished by incubation with tin protoporphyrin-IX and knock down of nuclear factor-E2-related factor 2.
  
  
  CONCLUSIONS
  Niacin activates HO-1 in vivo and in vitro. Induction of HO-1 may be partly responsible for the vascular protective properties of niacin.
authors.affiliation: Lipid Research Group, the Heart Research Institute, 7 Eliza St, Newtown, NSW, Australia, 2042. wub@hri.org.au
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Wu
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009525:Niacin / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits
chemical_list: D018836:Inflammation Mediators; D009525:Niacin; D051547:Heme Oxygenase-1