Reevaluation of the role of HDL in the anticoagulant activated protein C system in humans.
(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:
https://lup.lub.lu.se/record/1610559
- author
- Oslakovic, Cecilia LU ; Norstrøm, Eva and Dahlbäck, Björn LU
- organization
- publishing date
- 2010
- 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
- The 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
- 2016-04-04 09:27:43
- date last changed
- 2022-01-29 18:00:10
@article{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}},
keywords = {{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 = {{The American Society for Clinical Investigation}},
series = {{Journal of Clinical Investigation}},
title = {{Reevaluation of the role of HDL in the anticoagulant activated protein C system in humans.}},
url = {{https://lup.lub.lu.se/search/files/5330804/1627970.pdf}},
doi = {{10.1172/JCI42260}},
volume = {{120}},
year = {{2010}},
}