title: 2-chlorohexadecanal derived from hypochlorite-modified high-density lipoprotein-associated plasmalogen is a natural inhibitor of endothelial nitric oxide biosynthesis.
abstract: OBJECTIVE
  Myeloperoxidase, a heme enzyme that is present and active in human atherosclerotic lesions, provides a source for the generation of proinflammatory chlorinated reactants contributing to endothelial dysfunction. Modification of high-density lipoprotein (HDL) by hypochlorous acid/hypochlorite (HOCl/OCl-) [correction]-generated in vivo by the myeloperoxidase-hydrogen peroxide-chloride system of activated phagocytes-forms a proatherogenic lipoprotein particle that binds to and is internalized by endothelial cells.
  
  
  RESULTS
  Here we show that HDL, modified with physiologically relevant HOCl concentrations, attenuates the expression and activity of vasculoprotective endothelial nitric oxide synthase. HOCl-HDL promotes dislocalization of endothelial nitric oxide synthase from the plasma membrane and perinuclear location of human umbilical venous endothelial cells. We could identify 2-chlorohexadecanal as the active component mediating this inhibitory activity. This chlorinated fatty aldehyde is formed during HOCl-mediated oxidative cleavage of HDL-associated plasmalogen.
  
  
  CONCLUSIONS
  2-Chlorohexadecanal, produced by the myeloperoxidase-hydrogen peroxide-chloride system of activated phagocytes may act as a mediator of vascular injury associated with ischemia-reperfusion injury, glomerulosclerosis, and atherosclerosis.
authors.affiliation: Institute of Molecular Biology and Biochemistry, Medical University Graz, Austria.
authors.forename: Gunther
authors.initials: G
authors.lastname: Marsche
authors.forename: Regine
authors.initials: R
authors.lastname: Heller
authors.forename: Günter
authors.initials: G
authors.lastname: Fauler
authors.forename: Alenka
authors.initials: A
authors.lastname: Kovacevic
authors.forename: Alexander
authors.initials: A
authors.lastname: Nuszkowski
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Graier
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sattler
authors.forename: Ernst
authors.initials: E
authors.lastname: Malle
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D010955:Plasmalogens / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology / Q000201:enzymology / Q000378:metabolism
chemical_list: C432398:2-chlorohexadecanal; D000447:Aldehydes; D008075:Lipoproteins, HDL; D010955:Plasmalogens; D009569:Nitric Oxide; D006997:Hypochlorous Acid; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III