Reevaluation of the role of HDL in the anticoagulant activated protein C system in humans.
Author
Summary, in English
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.
Department/s
Publishing year
2010
Language
English
Pages
1396-1399
Publication/Series
Journal of Clinical Investigation
Volume
120
Issue
5
Full text
- Available as PDF - 194 kB
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Links
Document type
Journal article
Publisher
The American Society for Clinical Investigation
Topic
- Medicinal Chemistry
Keywords
- Thromboplastin: metabolism
- Protein C: metabolism
- Phospholipids: metabolism
- Liposomes: metabolism
- HDL: metabolism
- Lipoproteins
- Factor Xa: metabolism
- Factor Va: metabolism
- Annexin A5: metabolism
- Anticoagulants: metabolism
Status
Published
Research group
- Clinical Chemistry, Malmö
ISBN/ISSN/Other
- ISSN: 0021-9738