Linked Life Data

10521388

Source:http://linkedlifedata.com/resource/pubmed/id/10521388

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1999-10-29
pubmed:abstractText
The intimal thickening that follows vascular injury is inhibited by periprocedural tissue factor pathway inhibitor (TFPI) treatment in animal models. TFPI is a multivalent Kunitz-type protease inhibitor that inhibits factor Xa via its second Kunitz domain and the factor VIIa/tissue factor (TF) complex via its first Kunitz domain. The basic C-terminus of TFPI is required for the binding of TFPI to cell surfaces and cell-bound TFPI mediates the internalization and degradation of factor X and the down regulation of surface factor VIIa/TF activity. The C-terminus of TFPI is also required for its reported direct inhibition of smooth muscle cell proliferation in vitro. To examine the structural requirements for the inhibition of neointimal formation by TFPI, several TFPI-related proteins were tested in the rat carotid angioplasty model: 1) XK(1), a hybrid protein containing the N-terminal portion of factor X and the first Kunitz domain of TFPI that directly inhibits factor VIIa/TF; 2) TFPI(WT), the full-length TFPI molecule that inhibits factor Xa and factor VIIa/TF and binds cell surfaces; 3) TFPI(K36I), an altered form of TFPI that inhibits factor Xa, but not factor VIIa/TF, and binds cell surfaces; 4) TFPI(13-161), a truncated form of TFPI that inhibits factor VIIa/TF but interacts with factor Xa poorly and does not bind to cell surfaces. Seven day infusions of XK(1), TFPI(WT), and high levels of TFPI(K36I) begun the day before balloon-induced vascular injury produced a significant reduction in the intimal hyperplasia measured 28 days after angioplasty. The infusion of high concentrations of TFPI(13-161) was ineffective in this model. These in vivo results directly mirror the ability of each TFPI-related protein to inhibit tissue thromboplastin-induced coagulation in rat plasma: XK(1) approximately TFPI(WT)>TFPI(K36I)>>TFPI(13-161). The studies confirm the important role of TF-mediated coagulation in the smooth muscle proliferation and neointimal thickening that follows vascular injury and suggest that the anticoagulant effect alone of TFPI and TFPI-related proteins is sufficient to explain their therapeutic action.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1079-5642
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2563-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10521388-Angioplasty, Balloon, pubmed-meshheading:10521388-Animals, pubmed-meshheading:10521388-Carotid Artery, Common, pubmed-meshheading:10521388-Carotid Artery Injuries, pubmed-meshheading:10521388-Cricetinae, pubmed-meshheading:10521388-Disease Models, Animal, pubmed-meshheading:10521388-Factor VIIa, pubmed-meshheading:10521388-Female, pubmed-meshheading:10521388-Fibrinolytic Agents, pubmed-meshheading:10521388-Kidney, pubmed-meshheading:10521388-Lipoproteins, pubmed-meshheading:10521388-Peptide Fragments, pubmed-meshheading:10521388-Rats, pubmed-meshheading:10521388-Rats, Sprague-Dawley, pubmed-meshheading:10521388-Reagent Kits, Diagnostic, pubmed-meshheading:10521388-Recombinant Proteins, pubmed-meshheading:10521388-Thromboplastin, pubmed-meshheading:10521388-Tunica Intima
pubmed:year
1999
pubmed:articleTitle
Structural requirements for TFPI-mediated inhibition of neointimal thickening after balloon injury in the rat.
pubmed:affiliation
Division of Hematology/Oncology, Barnes-Jewish Hospital at Washington University Medical Center, St. Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't