|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 23, 19828-19835, June 8, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the We analyzed the influence of the atherogenic
oxidized low density lipoproteins (LDL) on the activity of the platelet
prothrombinase complex, a major contributor to overall thrombin
formation in vivo. Platelet dependent thrombin generation
was found to be strongly stimulated by in vitro oxidized
LDL. The enhancement was additive to that observed with the platelet
agonist thrombin. Oxidized LDL increased the platelet binding of
annexin-V, suggesting that the augmented surface exposure of
aminophospholipids promoted the prothrombinase activity. All of the
stimulatory activity of the oxidized LDL could be recovered in the
microemulsions prepared from the lipid portion of the modified
particles. Phospholipid vesicles were prepared containing the total
lipids of the oxidized LDL but lacking specifically in one lipid
component. Following the selective removal of the ethanolamine
phospholipids (PE) from the LDL lipids, the
platelet-dependent thrombin formation was markedly reduced.
Vesicles enriched with the isolated PE fraction alone enhanced the
thrombin generation. Analyses with autoxidized phospholipids indicated
that oxidation products of unsaturated diacyl-PE were mainly
responsible for the increased prothrombinase activity. Oxidized LDL and
its PE fraction lost their stimulatory activity after treatment with
NaCNBH3, a chemical reductant of Schiff base adducts.
Phospholipid vesicles supplemented with synthetic aldehyde-PE adducts
largely reproduced the stimulation of the thrombin generation. We
conclude that the oxidized LDL particles elicit a pronounced
prothrombotic response by increasing the activity of the platelet
prothrombinase complex. Specific oxidative modifications of the
LDL-associated ethanolamine phospholipids are mainly responsible for
this stimulation.
Modified Phosphatidylethanolamine as the Active Component of
Oxidized Low Density Lipoprotein Promoting Platelet
Prothrombinase Activity*
,,,¶
Physiologisches Institut der
Universität München, Schillerstrasse 44, 80336 München, Germany and § Institut für Biochemie
und Lebensmittelchemie, Technische Universität Graz, 8010 Graz, Austria
*
This study was supported by grants from the Deutsche
Forschungsgemeinschaft and the Friedrich-Baur-Stiftung (to B. E.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Tetik, F. Uras, E. Eksioglu-Demiralp, and K. Turay Yardimci Low-Density Lipoprotein Specifically Binds Glycoprotein IIb/IIIa: A Flow Cytometric Method for Ligand-Receptor Interaction Clinical and Applied Thrombosis/Hemostasis, April 1, 2008; 14(2): 210 - 219. [Abstract] [PDF]
|
|
|
|
 |
|
 P. Baumgartner, M. Geiger, S. Zieseniss, J. Malleier, J. A. Huntington, K. Hochrainer, E. Bielek, M. Stoeckelhuber, K. Lauber, D. Scherfeld, et al. Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor J. Cell Biol., November 19, 2007; 179(4): 793 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Moumtzi, M. Trenker, K. Flicker, E. Zenzmaier, R. Saf, and A. Hermetter Import and fate of fluorescent analogs of oxidized phospholipids in vascular smooth muscle cells J. Lipid Res., March 1, 2007; 48(3): 565 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Bruni, A. L. Pasqui, M. Pastorelli, G. Bova, M. Cercignani, A. Palazzuoli, T. Sawamura, A. Auteri, and L. Puccetti Different Effect of Statins on Platelet Oxidized-LDLReceptor (CD36 and LOX-1) Expressionin Hypercholesterolemic Subjects Clinical and Applied Thrombosis/Hemostasis, October 1, 2005; 11(4): 417 - 428. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Bhatnagar Cardiovascular pathophysiology of environmental pollutants Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H479 - H485. [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Ananyeva, D. V. Kouiavskaia, M. Shima, and E. L. Saenko Intrinsic pathway of blood coagulation contributes to thrombogenicity of atherosclerotic plaque Blood, May 29, 2002; 99(12): 4475 - 4485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kamido, H. Eguchi, H. Ikeda, T. Imaizumi, K. Yamana, K. Hartvigsen, A. Ravandi, and A. Kuksis Core aldehydes of alkyl glycerophosphocholines in atheroma induce platelet aggregation and inhibit endothelium-dependent arterial relaxation J. Lipid Res., January 1, 2002; 43(1): 158 - 166. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |