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Anionic Phospholipids Lose their Procoagulant Properties when Incorporated into High-Density Lipoproteins.

Oslakovic, Cecilia LU ; Krisinger, Michael LU ; Andersson, Astra LU ; Jauhiainen, Matti; Ehnholm, Christian and Dahlbäck, Björn LU (2009) In Journal of Biological Chemistry 284(9). p.5896-5904
Abstract
Blood coagulation involves a series of enzymatic protein complexes that assemble on the surface of anionic phospholipid. To investigate whether apolipoproteins affect coagulation reactions, they where included during the preparation of anionic phospholipid vesicles using a detergent solubilization-dialysis method. Apolipoprotein components of high-density lipoproteins, especially apolipoprotein A-I, had pronounced anticoagulant effect. The anionic phospholipids lost their procoagulant effect when the vesicle preparation method was performed in the presence of apolipoprotein A-I. The anionic phospholipid-apolipoprotein A-I particles were 8-10 nm in diameter and contained around 60-80 phospholipid molecules, depending on the phospholipid... (More)
Blood coagulation involves a series of enzymatic protein complexes that assemble on the surface of anionic phospholipid. To investigate whether apolipoproteins affect coagulation reactions, they where included during the preparation of anionic phospholipid vesicles using a detergent solubilization-dialysis method. Apolipoprotein components of high-density lipoproteins, especially apolipoprotein A-I, had pronounced anticoagulant effect. The anionic phospholipids lost their procoagulant effect when the vesicle preparation method was performed in the presence of apolipoprotein A-I. The anionic phospholipid-apolipoprotein A-I particles were 8-10 nm in diameter and contained around 60-80 phospholipid molecules, depending on the phospholipid composition. The phospholipids of these particles were unable to support the activation of prothrombin by factor Xa in the presence of factor Va, and unable to support binding of factor Va, while binding of prothrombin and factor Xa were efficient. Phospholipid transfer protein was shown to mediate transfer of phospholipids from liposomes to apolipoprotein A-I containing reconstituted high-density lipoprotein. In addition, serum was also shown to neutralize the procoagulant effect of anionic liposomes and to efficiently mediate transfer of phospholipids from liposomes to either apolipoprotein A-I or apolipoprotein B containing particles. In conclusion, apolipoprotein A-I was found to neutralize the procoagulant properties of anionic phospholipids by arranging the phospholipids in surface areas that are too small to accommodate the prothrombinase complex. This anionic phospholipid scavenger function may be an important mechanism to control the exposure of such phospholipids to circulating blood and thereby prevent inappropriate stimulation of blood coagulation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
284
issue
9
pages
5896 - 5904
publisher
ASBMB
external identifiers
  • wos:000263560600053
  • pmid:19129179
  • scopus:65549154392
ISSN
1083-351X
DOI
10.1074/jbc.M807286200
language
English
LU publication?
yes
id
ec33e15d-9944-4b92-9035-13db47ef8059 (old id 1289859)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19129179?dopt=Abstract
date added to LUP
2009-02-03 10:12:54
date last changed
2017-04-16 04:19:51
@article{ec33e15d-9944-4b92-9035-13db47ef8059,
  abstract     = {Blood coagulation involves a series of enzymatic protein complexes that assemble on the surface of anionic phospholipid. To investigate whether apolipoproteins affect coagulation reactions, they where included during the preparation of anionic phospholipid vesicles using a detergent solubilization-dialysis method. Apolipoprotein components of high-density lipoproteins, especially apolipoprotein A-I, had pronounced anticoagulant effect. The anionic phospholipids lost their procoagulant effect when the vesicle preparation method was performed in the presence of apolipoprotein A-I. The anionic phospholipid-apolipoprotein A-I particles were 8-10 nm in diameter and contained around 60-80 phospholipid molecules, depending on the phospholipid composition. The phospholipids of these particles were unable to support the activation of prothrombin by factor Xa in the presence of factor Va, and unable to support binding of factor Va, while binding of prothrombin and factor Xa were efficient. Phospholipid transfer protein was shown to mediate transfer of phospholipids from liposomes to apolipoprotein A-I containing reconstituted high-density lipoprotein. In addition, serum was also shown to neutralize the procoagulant effect of anionic liposomes and to efficiently mediate transfer of phospholipids from liposomes to either apolipoprotein A-I or apolipoprotein B containing particles. In conclusion, apolipoprotein A-I was found to neutralize the procoagulant properties of anionic phospholipids by arranging the phospholipids in surface areas that are too small to accommodate the prothrombinase complex. This anionic phospholipid scavenger function may be an important mechanism to control the exposure of such phospholipids to circulating blood and thereby prevent inappropriate stimulation of blood coagulation.},
  author       = {Oslakovic, Cecilia and Krisinger, Michael and Andersson, Astra and Jauhiainen, Matti and Ehnholm, Christian and Dahlbäck, Björn},
  issn         = {1083-351X},
  language     = {eng},
  number       = {9},
  pages        = {5896--5904},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Anionic Phospholipids Lose their Procoagulant Properties when Incorporated into High-Density Lipoproteins.},
  url          = {http://dx.doi.org/10.1074/jbc.M807286200},
  volume       = {284},
  year         = {2009},
}