Source:http://linkedlifedata.com/resource/pubmed/id/12062545
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
|
pubmed:dateCreated |
2002-6-13
|
pubmed:abstractText |
Protein S (PS) is a vitamin K-dependent plasma protein and serves as a cofactor for the anticoagulant activities of activated protein C (APC). We investigated the effects of different PS concentrations on prothrombin activation and thrombin generation in cord and adult plasma containing APC and different amounts of alpha 2-macroglobulin (a2-M). Prothrombin activation was assessed by monitoring the time-course of prothrombin fragment 1+2 (F1+2) generation. Thrombin generation curves were determined by means of a subsampling technique using the chromogenic substrate S-2238. We demonstrate a dose-dependent inhibition of the anticoagulant action of PS by a2-M: suppression of F1+2 and thrombin generation due to addition of PS was stronger in plasma containing low amounts of a2-M than in plasma with elevated a2-M levels. Since no complex formation between a2-M and PS was observed by means of SDS-PAGE, we attribute decreased anticoagulant action of PS at high a2-M levels to enhanced complex formation between APC and a2-M. Thereby, APC is subtracted from its cofactor PS, resulting in suppressed formation of the anticoagulant APC/PS complex. Thus, our data suggest that a2-M, besides its well-known anticoagulant effects, also acts as a procoagulant by suppressing the formation of the anticoagulant APC/PS complex. Our findings have implications particularly on thrombin generation and inhibition in cord plasma, since a2-M levels in newborns are elevated over adult values and the antithrombotic APC/PS pathway is up-regulated at birth. Therefore, elevated levels of a2-M might restrict the up-regulation of the APC/PS pathway.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Protein C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein S,
http://linkedlifedata.com/resource/pubmed/chemical/Prothrombin,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Macroglobulins
|
pubmed:status |
MEDLINE
|
pubmed:month |
Mar
|
pubmed:issn |
0049-3848
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
1
|
pubmed:volume |
105
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
433-9
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:12062545-Adult,
pubmed-meshheading:12062545-Dose-Response Relationship, Drug,
pubmed-meshheading:12062545-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:12062545-Fetal Blood,
pubmed-meshheading:12062545-Humans,
pubmed-meshheading:12062545-Infant, Newborn,
pubmed-meshheading:12062545-Kinetics,
pubmed-meshheading:12062545-Protein C,
pubmed-meshheading:12062545-Protein S,
pubmed-meshheading:12062545-Prothrombin,
pubmed-meshheading:12062545-Thrombin,
pubmed-meshheading:12062545-alpha-Macroglobulins
|
pubmed:year |
2002
|
pubmed:articleTitle |
Alpha 2-macroglobulin enhances prothrombin activation and thrombin potential by inhibiting the anticoagulant protein C/protein S system in cord and adult plasma.
|
pubmed:affiliation |
Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Graz, Austria. gerhard.cvirn@klinikum-graz.at
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|