Source:http://linkedlifedata.com/resource/pubmed/id/15292065
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2004-11-19
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pubmed:abstractText |
The activated protein C (APC)-independent anticoagulant activity of protein S on tissue factor-induced thrombin generation was quantified in plasma. In absence of APC, protein S significantly decreased the endogenous thrombin potential (ETP) in a concentration-dependent manner. The APC-independent anticoagulant activity of protein S in plasma was not affected by phospholipid concentrations but strongly depended on tissue factor concentrations: protein S inhibited the ETP from 6% at 140 pM tissue factor to 74% at 1.4 pM tissue factor. Plasma with both 60% protein S and 140% prothrombin showed an ETP of 240% compared to normal plasma, suggesting an APC-independent protective role of protein S in the development of thrombosis as a result of protein S deficiency and the prothrombin-G20210A mutation. At high tissue-factor concentrations, protein S hardly expressed APC-independent anticoagulant activity but exerted potent APC-cofactor activity when thrombomodulin or APC were added to plasma. Neutralization of protein S under these conditions resulted in a 20-fold reduction of the anticoagulant activity of APC. The present study shows that protein S effectively regulates coagulation at 2 levels: at low procoagulant stimuli, protein S maintains the hemostatic balance by directly inhibiting thrombin formation, and at high procoagulant stimuli, protein S restores the hemostatic balance via its APC-cofactor activity.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Protein C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein S,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombomodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Thromboplastin
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
104
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3624-30
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15292065-Adult,
pubmed-meshheading:15292065-Blood Coagulation,
pubmed-meshheading:15292065-Dose-Response Relationship, Drug,
pubmed-meshheading:15292065-Female,
pubmed-meshheading:15292065-Hemostasis,
pubmed-meshheading:15292065-Humans,
pubmed-meshheading:15292065-Male,
pubmed-meshheading:15292065-Middle Aged,
pubmed-meshheading:15292065-Phospholipids,
pubmed-meshheading:15292065-Plasma,
pubmed-meshheading:15292065-Protein C,
pubmed-meshheading:15292065-Protein S,
pubmed-meshheading:15292065-Thrombin,
pubmed-meshheading:15292065-Thrombomodulin,
pubmed-meshheading:15292065-Thromboplastin
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pubmed:year |
2004
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pubmed:articleTitle |
Inhibition of thrombin generation by protein S at low procoagulant stimuli: implications for maintenance of the hemostatic balance.
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pubmed:affiliation |
Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, 6200 MD Maastricht, the Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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