Linked Life Data

9930309

Source:http://linkedlifedata.com/resource/pubmed/id/9930309

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1999-2-26
pubmed:abstractText
Metalloproteinases (MMPs) are implicated in neointima formation and hence vein graft failure. Gene transfer to elevate local levels of tissue inhibitor of metalloproteinases (TIMPs) is therefore a potential treatment. In this study, we have used lumenal application of a replication-defective recombinant adenovirus to overexpress TIMP-2 and observe the effects on neointimal thickening in a well characterised human saphenous vein organ culture model. Increased TIMP-2 expression was localised to lumenal surface cells but nevertheless increased total functional TIMP-2 secretion after 14 days culture from 4.0 +/- 2.0 to 21.8 +/- 2.9 ng/mg wet weight/day (P < 0.05, n = 3). In situ zymography revealed a marked inhibition of gelatinolytic activity by TIMP-2 gene transfer throughout the vein segments. Neointima formation and neointimal cell numbers were reduced 79% and 71%, respectively (P < 0.05; n = 8). TIMP-2 overexpression had no effect on smooth muscle cell proliferation, secretion of pro-MMP-2 or -9 and did not inhibit the processing of pro-MMP-2 to its active form. Our data indicate that TIMP-2 overexpression reduces neointimal thickening, primarily by inhibiting MMP activity and hence smooth muscle cell migration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1552-60
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Gene transfer of tissue inhibitor of metalloproteinase-2 inhibits metalloproteinase activity and neointima formation in human saphenous veins.
pubmed:affiliation
Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't