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Reevaluation of the role of HDL in the anticoagulant activated protein C system in humans.

Oslakovic, Cecilia LU ; Norstrøm, Eva and Dahlbäck, Björn LU (2010) In Journal of Clinical Investigation 120(5). p.1396-1399
Abstract
HDL has anti-atherogenic properties, and plasma levels of HDL cholesterol correlate inversely with risk of coronary artery disease. HDL reportedly functions as a cofactor to the anticoagulant activated protein C (APC) in the degradation of factor Va (FVa). The aim of the present study was to elucidate the mechanism by which HDL functions as cofactor to APC. Consistent with a previous report, HDL isolated from human plasma by ultracentrifugation was found to stimulate APC-mediated degradation of FVa. However, further purification of HDL by gel filtration revealed that the stimulating activity was not a property of HDL. Instead, the stimulating activity eluted completely separately from HDL in the high-molecular-weight void volume fractions.... (More)
HDL has anti-atherogenic properties, and plasma levels of HDL cholesterol correlate inversely with risk of coronary artery disease. HDL reportedly functions as a cofactor to the anticoagulant activated protein C (APC) in the degradation of factor Va (FVa). The aim of the present study was to elucidate the mechanism by which HDL functions as cofactor to APC. Consistent with a previous report, HDL isolated from human plasma by ultracentrifugation was found to stimulate APC-mediated degradation of FVa. However, further purification of HDL by gel filtration revealed that the stimulating activity was not a property of HDL. Instead, the stimulating activity eluted completely separately from HDL in the high-molecular-weight void volume fractions. The active portion of these fractions stimulated FVa degradation by APC and supported the assembly of factor Xa and FVa into a functional prothrombinase complex. Both the procoagulant and anticoagulant activities were blocked by addition of annexin V, suggesting that the active portion was negatively charged phospholipid membranes. These results demonstrate that HDL does not stimulate the APC/protein S effect and that the activity previously reported to be a property of HDL is instead caused by contaminating negatively charged phospholipid membranes. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Thromboplastin: metabolism, Protein C: metabolism, Phospholipids: metabolism, Liposomes: metabolism, HDL: metabolism, Lipoproteins, Factor Xa: metabolism, Factor Va: metabolism, Annexin A5: metabolism, Anticoagulants: metabolism
in
Journal of Clinical Investigation
volume
120
issue
5
pages
1396 - 1399
publisher
American Society for Clinical Investigation
external identifiers
  • WOS:000277248000009
  • PMID:20446351
  • Scopus:77951862815
ISSN
0021-9738
DOI
10.1172/JCI42260
language
English
LU publication?
yes
id
b9e70be2-e939-4263-9491-5d94ee2565fd (old id 1610559)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20446351?dopt=Abstract
date added to LUP
2010-06-01 20:48:38
date last changed
2016-11-18 12:42:04
@misc{b9e70be2-e939-4263-9491-5d94ee2565fd,
  abstract     = {HDL has anti-atherogenic properties, and plasma levels of HDL cholesterol correlate inversely with risk of coronary artery disease. HDL reportedly functions as a cofactor to the anticoagulant activated protein C (APC) in the degradation of factor Va (FVa). The aim of the present study was to elucidate the mechanism by which HDL functions as cofactor to APC. Consistent with a previous report, HDL isolated from human plasma by ultracentrifugation was found to stimulate APC-mediated degradation of FVa. However, further purification of HDL by gel filtration revealed that the stimulating activity was not a property of HDL. Instead, the stimulating activity eluted completely separately from HDL in the high-molecular-weight void volume fractions. The active portion of these fractions stimulated FVa degradation by APC and supported the assembly of factor Xa and FVa into a functional prothrombinase complex. Both the procoagulant and anticoagulant activities were blocked by addition of annexin V, suggesting that the active portion was negatively charged phospholipid membranes. These results demonstrate that HDL does not stimulate the APC/protein S effect and that the activity previously reported to be a property of HDL is instead caused by contaminating negatively charged phospholipid membranes.},
  author       = {Oslakovic, Cecilia and Norstrøm, Eva and Dahlbäck, Björn},
  issn         = {0021-9738},
  keyword      = {Thromboplastin: metabolism,Protein C: metabolism,Phospholipids: metabolism,Liposomes: metabolism,HDL: metabolism,Lipoproteins,Factor Xa: metabolism,Factor Va: metabolism,Annexin A5: metabolism,Anticoagulants: metabolism},
  language     = {eng},
  number       = {5},
  pages        = {1396--1399},
  publisher    = {ARRAY(0x8b3c860)},
  series       = {Journal of Clinical Investigation},
  title        = {Reevaluation of the role of HDL in the anticoagulant activated protein C system in humans.},
  url          = {http://dx.doi.org/10.1172/JCI42260},
  volume       = {120},
  year         = {2010},
}