title: High-density lipoproteins inhibit vascular endothelial inflammation by increasing 3β-hydroxysteroid-Δ24 reductase expression and inducing heme oxygenase-1.
abstract: BACKGROUND
  Lipid-free apolipoprotein (apo) A-I and discoidal reconstituted high-density lipoproteins (rHDL) containing apoA-I, (A-I)rHDL, inhibit vascular inflammation by increasing 3β-hydroxysteroid-Δ24 reductase (DHCR24) expression.
  
  
  OBJECTIVE
  To determine whether the lipid-free apoA-I-mediated and (A-I)rHDL-mediated increase in DHCR24 expression induces the cytoprotective and potentially cardioprotective enzyme, heme oxygenase-1 (HO-1).
  
  
  RESULTS
  In vivo: A single intravenous infusion of lipid-free apoA-I (8 mg/kg) administered 24 hours before inserting a nonocclusive periarterial carotid collar into New Zealand White rabbits decreased collar-induced endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression, reduced intima/media neutrophil infiltration, and increased DHCR24 and HO-1 mRNA levels. Knockdown of vascular DHCR24 and HO-1 and systemic administration of tin-protoporphyrin-IX, an HO inhibitor, abolished these anti-inflammatory effects. In vitro: Preincubation of human coronary artery endothelial cells with (A-I)rHDL before activation with tumor necrosis factor-α increased DHCR24 and HO-1 mRNA levels and inhibited cytokine-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression. Transfection of the cells with DHCR24 and HO-1 small interfering RNA and tin-protoporphyrin-IX treatment abolished these effects. The (A-I)rHDL-mediated induction of HO-1 was reduced in human coronary artery endothelial cells transfected with DHCR24 small interfering RNA. Transfection of human coronary artery endothelial cells with HO-1 small interfering RNA and tin-protoporphyrin-IX treatment did not inhibit the (A-I)rHDL-mediated increase in DHCR24 expression. Inhibition of phosphatidylinositol 3-kinase/Akt reduced the (A-I)rHDL-mediated increase in HO-1, but not DHCR24 expression. The activation of phosphatidylinositol 3-kinase/Akt by (A-I)rHDL was decreased in human coronary artery endothelial cells that were transfected with DHCR24 small interfering RNA.
  
  
  CONCLUSIONS
  Lipid-free apoA-I and (A-I)rHDL inhibit inflammation by increasing DHCR24 expression, which, in turn, activates phosphatidylinositol 3-kinase/Akt and induces HO-1.
authors.affiliation: Lipid Research Group, The Heart Research Institute, 7 Eliza St, Newtown, Sydney, New South Wales 2042, Australia. 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: Sudichhya
authors.initials: S
authors.lastname: Shrestha
authors.forename: Kwok L
authors.initials: KL
authors.lastname: Ong
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000473:pathology*; D004790:Enzyme Induction / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D008075:Lipoproteins, HDL / Q000502:physiology* / Q000627:therapeutic use; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000096:biosynthesis* / Q000235:genetics; D011817:Rabbits; D014657:Vasculitis / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control
chemical_list: D008075:Lipoproteins, HDL; D009419:Nerve Tissue Proteins; D051547:Heme Oxygenase-1; D044925:Oxidoreductases Acting on CH-CH Group Donors; C437069:3beta-hydroxysterol delta24-reductase