Plasma phospholipid transfer protein deficiency in mice is associated with a reduced thrombotic response to acute intravascular oxidative stress.
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.
Desrumaux
Catherine
C
Institut National de la Santé et de la Recherche Médicale, UMR866, Dijon, France.
Deckert
Valérie
V
Lemaire-Ewing
Stéphanie
S
Mossiat
Claude
C
Athias
Anne
A
Vandroux
David
D
Dumont
Laure
L
Monier
Serge
S
Pais de Barros
Jean-Paul
JP
Klein
Alexis
A
De Maistre
Emmanuel
E
Blache
Denis
D
Beley
Alain
A
Marie
Christine
C
Garnier
Philippe
P
Lagrost
Laurent
L
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
D008041:Linoleic Acids; D049294:Phospholipid Transfer Proteins; D014665:Vasodilator Agents; C510091:phospholipid transfer protein, mouse; D024502:alpha-Tocopherol