Linked Life Data

10764685

Source:http://linkedlifedata.com/resource/pubmed/id/10764685

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-4-27
pubmed:abstractText
The serine protease thrombin is a mitogen for vascular smooth muscle cells. To that end, thrombin cleaves the surface-exposed, protease-activated receptor type 1 (PAR-1), resulting in signal transduction and ultimately, proliferation of these cells. Regulation of thrombin activity in the human atherosclerotic vessel wall has not been studied in great detail, conceivably because the traditional plasma thrombin inhibitor, anti-thrombin III, is not encountered at this location. By using immunofluorescence confocal microscopy, we demonstrate that the antigens of thrombin, plasminogen activator inhibitor 1 (PAI-1), and vitronectin (Vn) colocalize in human neointimal atherosclerotic arterial tissue. Furthermore, it is shown by in situ reverse zymography that these specimens harbor the active form of PAI-1, which is the only configuration of PAI-1 capable of complexing with Vn and inhibiting serine proteases, eg, thrombin. Two different criteria were used to establish that neointimal atherosclerotic material contains active alpha-thrombin, namely, its ability to bind to the thrombin inhibitor hirudin and to convert the thrombin-specific chromogenic substrate S2238. The latter activity could be fully prevented by preincubation with the thrombin-specific inhibitor, phenyl-prolyl-arginyl-chloromethyl ketone. The thrombin concentration measured by conversion of the chromogenic substrate was 7 to 12 nmol/L in the vascular specimens studied. This concentration range suffices to activate the PAR-1 receptor on vascular smooth muscle cells and to cause neointimal proliferation. It is concluded that the human atherosclerotic arterial vessel wall provides conditions that favor a regulatory mechanism of thrombin activity by PAI-1/Vn complexes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1079-5642
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1143-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Colocalization of thrombin, PAI-1, and vitronectin in the atherosclerotic vessel wall: A potential regulatory mechanism of thrombin activity by PAI-1/vitronectin complexes.
pubmed:affiliation
Department of Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.a.stoop@amc.uva.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't