title: Plasma phospholipid transfer protein deficiency in mice is associated with a reduced thrombotic response to acute intravascular oxidative stress.
abstract: OBJECTIVE
  Earlier in vitro studies suggested a putative role for the plasma phospholipid transfer protein (PLTP) in the modulation of blood coagulation. The effect of PLTP expression on blood coagulation under both basal and oxidative stress conditions was compared here in wild-type and PLTP-deficient (PLTP-/-) mice.
  
  
  RESULTS
  Under basal conditions, PLTP deficiency was associated with an extended tail bleeding time despite a significant depletion of vascular α-tocopherol content and an impairment of endothelial function. When acute oxidative stress was generated in vivo in the brain vasculature, the steady state levels of oxidized lipid derivatives, the extent of blood vessel occlusion, and the volume of ischemic lesions were more severe in wild-type than in PLTP-/- mice.
  
  
  CONCLUSIONS
  In addition to its recognized hyperlipidemic, proinflammatory, and proatherogenic properties, PLTP increases blood coagulation and worsens the extent of ischemic lesions in response to acute oxidative stress. Thus, PLTP arises here as a cardiovascular risk factor for the late thrombotic events occurring in the acute phase of atherosclerosis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR866, Dijon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Desrumaux
authors.forename: Valérie
authors.initials: V
authors.lastname: Deckert
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lemaire-Ewing
authors.forename: Claude
authors.initials: C
authors.lastname: Mossiat
authors.forename: Anne
authors.initials: A
authors.lastname: Athias
authors.forename: David
authors.initials: D
authors.lastname: Vandroux
authors.forename: Laure
authors.initials: L
authors.lastname: Dumont
authors.forename: Serge
authors.initials: S
authors.lastname: Monier
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Pais de Barros
authors.forename: Alexis
authors.initials: A
authors.lastname: Klein
authors.forename: Emmanuel
authors.initials: E
authors.lastname: De Maistre
authors.forename: Denis
authors.initials: D
authors.lastname: Blache
authors.forename: Alain
authors.initials: A
authors.lastname: Beley
authors.forename: Christine
authors.initials: C
authors.lastname: Marie
authors.forename: Philippe
authors.initials: P
authors.lastname: Garnier
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
mesh_terms: D000818:Animals; D001760:Bleeding Time; D001777:Blood Coagulation; D002544:Cerebral Infarction / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D020767:Intracranial Thrombosis / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008041:Linoleic Acids / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D049294:Phospholipid Transfer Proteins / Q000172:deficiency* / Q000235:genetics; D014665:Vasodilator Agents / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000097:blood
chemical_list: D008041:Linoleic Acids; D049294:Phospholipid Transfer Proteins; D014665:Vasodilator Agents; C510091:phospholipid transfer protein, mouse; D024502:alpha-Tocopherol