Linked Life Data

11193216

Source:http://linkedlifedata.com/resource/pubmed/id/11193216

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-1-19
pubmed:abstractText
Proteolysis of vascular basement membranes and surrounding extracellular matrix is a critical early step in neovascularization. It requires alteration of the balance between matrix metalloproteinases (MMPs) and proteins that bind to and inactivate MMPs, tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 has been demonstrated to inhibit neovascularization in chick chorioallantoic membranes. However, TIMP-1 has also been shown to either promote or inhibit cell proliferation and migration in different settings. To determine whether genetic alteration of the MMP/TIMP-1 ratio would alter retinal neovascularization, we crossed mice that express vascular endothelial growth factor (VEGF) in photoreceptors with TIMP-1-deficient mice or mice that overexpress TIMP-1. Compared to VEGF transgene-positive/TIMP-1-sufficient mice, VEGF transgene-positive/TIMP-1-deficient mice showed smaller neovascular lesions. There was also no difference between the two groups of mice in the appearance of the neovascularization by light or electron microscopy. Compound VEGF/TIMP-1 transgenic mice had increased expression of both VEGF and TIMP-1 in the retina, and had more neovascularization than mice that had increased expression of VEGF alone. These gain- and loss-of-function data suggest that alteration of the TIMP-1/MMP ratio modulates retinal neovascularization in a complex manner and not simply by altering the proteolytic activity and thereby invasiveness of endothelial cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0213-3911
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
87-97
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11193216-Actins, pubmed-meshheading:11193216-Animals, pubmed-meshheading:11193216-Blotting, Northern, pubmed-meshheading:11193216-Blotting, Southern, pubmed-meshheading:11193216-Drug Synergism, pubmed-meshheading:11193216-Endothelial Growth Factors, pubmed-meshheading:11193216-Lymphokines, pubmed-meshheading:11193216-Mice, pubmed-meshheading:11193216-Mice, Transgenic, pubmed-meshheading:11193216-Microscopy, Electron, pubmed-meshheading:11193216-Neovascularization, Physiologic, pubmed-meshheading:11193216-Retinal Vessels, pubmed-meshheading:11193216-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11193216-Tissue Inhibitor of Metalloproteinase-1, pubmed-meshheading:11193216-Vascular Endothelial Growth Factor A, pubmed-meshheading:11193216-Vascular Endothelial Growth Factors
pubmed:year
2001
pubmed:articleTitle
TIMP-1 promotes VEGF-induced neovascularization in the retina.
pubmed:affiliation
The Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-9277, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't