Source:http://linkedlifedata.com/resource/pubmed/id/17234207
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2007-3-12
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| pubmed:abstractText |
Tissue factor (TF) initiates the protease coagulation cascade in response to tissue injury. Homozygous deficiency of murine TF results in embryonic lethality, which is rescued by low-level expression of human TF. These low-TF mice have been shown to develop cardiac fibrosis. We tested the hypothesis that the development of cardiac fibrosis in low-TF mice results from dysregulated protease expression and is affected by gender. Mice were divided into the age groups 2-5, 6-12, 13-18 and 19+ weeks. Fibrosis was assessed by trichrome staining. Protease expression was measured in male and female mice by RT-PCR for mRNA and zymography, ELISA or immunoblot for protein. Urokinase plasminogen activator (uPA) activity was determined by zymography and chromogenic substrate assay. A marked gender effect was noted for the development of fibrosis, with interstitial collagen deposition occurring from 9 weeks in male low-TF mice, but not until 19 weeks in low-TF females. This delayed onset in females was accompanied by delayed up-regulation of molecular markers of injury. Matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 expression were up-regulated in the hearts of male low-TF mice from 6 to 12 weeks and in females from 19 weeks. MMP/TIMP dysregulation was not seen prior to cardiac fibrosis and did not appear to explain the gender differences. However, uPA expression and activity were down-regulated prior to cardiac fibrosis in low-TF females, but were up-regulated in age-matched males. This suggests that the down-regulation of uPA in female low-TF mice protects them from more severe cardiac fibrosis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/CTGF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Connective Tissue Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Ctgf protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Thromboplastin,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Inhibitor of...,
http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0022-2828
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
42
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
559-71
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:17234207-Animals,
pubmed-meshheading:17234207-Biological Markers,
pubmed-meshheading:17234207-Connective Tissue Growth Factor,
pubmed-meshheading:17234207-Down-Regulation,
pubmed-meshheading:17234207-Endomyocardial Fibrosis,
pubmed-meshheading:17234207-Female,
pubmed-meshheading:17234207-Humans,
pubmed-meshheading:17234207-Immediate-Early Proteins,
pubmed-meshheading:17234207-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:17234207-Male,
pubmed-meshheading:17234207-Matrix Metalloproteinases,
pubmed-meshheading:17234207-Mice,
pubmed-meshheading:17234207-Mice, Inbred C57BL,
pubmed-meshheading:17234207-Mice, Transgenic,
pubmed-meshheading:17234207-Oxidative Stress,
pubmed-meshheading:17234207-RNA, Messenger,
pubmed-meshheading:17234207-Sex Characteristics,
pubmed-meshheading:17234207-Thromboplastin,
pubmed-meshheading:17234207-Tissue Inhibitor of Metalloproteinases,
pubmed-meshheading:17234207-Up-Regulation,
pubmed-meshheading:17234207-Urokinase-Type Plasminogen Activator
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| pubmed:year |
2007
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| pubmed:articleTitle |
The development of cardiac fibrosis in low tissue factor mice is gender-dependent and is associated with differential regulation of urokinase plasminogen activator.
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| pubmed:affiliation |
Renal Research Laboratory, University of New South Wales, Level 2, Clinical Sciences Building, Prince of Wales Hospital, Randwick, NSW 2031, Australia. dr.darrendavis@gmail.com <dr.darrendavis@gmail.com>
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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