title: Induction of haemeoxygenase-1 improves FFA-induced endothelial dysfunction in rat aorta.
abstract: BACKGROUND
  The induction of haemeoxygenase-1 (HO-1) exerts beneficial effects in the setting of endothelial dysfunction in obesity. High free fatty acid (FFA) levels are a common feature of obesity and are the primary cause of endothelial dysfunction. The objective of our study was to explore the effects of HO-1 induction on FFA-induced endothelial dysfunction in rats.
  
  
  METHODS
  Rats received FFA treatment with either cobalt protoporphyrin (CoPP) to induce HO-1 or stannous protoporphyrin (SnPP) to inhibit HO-1. Endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV). Nitric oxide (NO) production, superoxide production and nuclear factor (NF)-κB expression in the aorta were each determined. The levels of adenosine monophosphate (AMP)-activated kinase (AMPK) and endothelial nitric oxide synthase (eNOS) expression in endothelial cells were determined via Western blotting.
  
  
  RESULTS
  Induction of HO-1 by CoPP decreased circulating FFA, high-sensitivity C-reactive protein and malondialdehyde levels and increased serum adiponectin and glutathione levels compared with the FFA group (P<0.05). High FFA levels resulted in EDV impairment, which was improved by HO-1 induction (P<0.05). Induction of HO-1 increased NO levels and reduced aortic superoxide production and NF-κB expression compared with the FFA group. The FFA group exhibited decreased AMPK expression and eNOS phosphorylation, both of which were enhanced via HO-1 induction (P<0.05). The beneficial effects of CoPP on EDV were partially attenuated in vitro in the presence of inhibitors of AMPK, phosphatidylinositol 3-kinase (PI3K), and eNOS.
  
  
  CONCLUSIONS
  HO-1 induction with CoPP improves FFA-induced endothelial dysfunction in the rat aorta. The protective mechanism appears to be related to the activation of the AMPK-PI3K-eNOS pathway as a result of increased adiponectin levels as well as decreased inflammation and oxidative stress.
authors.affiliation: Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Hui
authors.forename: Shuxian
authors.initials: S
authors.lastname: Zhang
authors.forename: Ningning
authors.initials: N
authors.lastname: Hou
authors.forename: Yali
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis; D052242:Adiponectin / Q000097:blood; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism* / Q000473:pathology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008665:Metalloporphyrins / Q000008:administration & dosage; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D011524:Protoporphyrins / Q000008:administration & dosage; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D008665:Metalloporphyrins; D016328:NF-kappa B; D011524:Protoporphyrins; D013481:Superoxides; D009569:Nitric Oxide; C007095:cobaltiprotoporphyrin; D002097:C-Reactive Protein; C032628:tin protoporphyrin IX; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051547:Heme Oxygenase-1; D055372:AMP-Activated Protein Kinases