Source:http://linkedlifedata.com/resource/pubmed/id/16284278
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2006-2-23
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pubmed:abstractText |
Plasminogen activators (PAs; e.g., tissue-type, tPA) coupled to red blood cells (RBCs) display in vivo features useful for thromboprophylaxis: prolonged circulation, minimal extravasation, and preferential lysis of nascent versus preexisting clots. Yet, factors controlling the activity of RBC-bound PAs in vivo are not defined and may not mirror the profile of soluble PAs. We tested the role of RBC/PA binding to fibrin in fibrinolysis. RBC/tPA and RBC/tPA variant with low fibrin affinity (rPA) bound to and lysed plasminogen-containing fibrin clots in vitro comparably. In contrast, when coinjected in mice with fibrin emboli lodging in pulmonary vasculature, only RBC/tPA accumulated in lungs, which resulted in a more extensive fibrinolysis versus RBC/rPA (p < 0.01). Reconciling this apparent divergence between in vitro and in vivo behaviors, RBC/tPA, but not RBC/rPA perfused over fibrin in vitro at physiological shear stress bound to fibrin clots and caused greater fibrinolysis versus RBC/rPA (p < 0.001). These results indicate that because of high fibrin affinity, RBC/tPA binding to clots endures hemodynamic stress, which enhances fibrinolysis. Behavior of RBC/PAs under hemodynamic pressure is an important predictor of their performance in vivo.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
316
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1130-6
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16284278-Animals,
pubmed-meshheading:16284278-Erythrocytes,
pubmed-meshheading:16284278-Fibrin,
pubmed-meshheading:16284278-Fibrinolysis,
pubmed-meshheading:16284278-Hemodynamics,
pubmed-meshheading:16284278-Humans,
pubmed-meshheading:16284278-Male,
pubmed-meshheading:16284278-Mice,
pubmed-meshheading:16284278-Mice, Inbred C57BL,
pubmed-meshheading:16284278-Protein Binding,
pubmed-meshheading:16284278-Pulmonary Embolism,
pubmed-meshheading:16284278-Tissue Plasminogen Activator
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pubmed:year |
2006
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pubmed:articleTitle |
Fibrin affinity of erythrocyte-coupled tissue-type plasminogen activators endures hemodynamic forces and enhances fibrinolysis in vivo.
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pubmed:affiliation |
Institute for Environmental Medicine, University of Pennsylvania School of Medicine, One John Morgan Bldg., 3620 Hamilton Walk, Philadelphia, PA 19104-6068, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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