Linked Life Data

10708958

Source:http://linkedlifedata.com/resource/pubmed/id/10708958

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2000-5-11
pubmed:abstractText
Based on diverse evidence in animals and humans, it has been hypothesized that atherosclerosis, and other injury-induced hyperplasias such as restenosis, may result from a failure in endogenous inhibitory systems that normally limit wound repair and induce regression of wound repair cells. A key defect in one of these inhibitory pathways, the TGF-beta system, has been identified and characterized in both animal models and in human lesions and lesion-derived cells. Cells derived from human lesions are resistant to the antiproliferative and apoptotic effects of TGF-beta, while their normal counterparts from the vascular media are potently inhibited and killed. Both cell types increase PAI-1 production, switch actin phenotypes in response to TGF-beta1, and produce similar levels of TGF-beta activity. Membrane cross-linking of (125)I-TGF-beta1 indicates that normal human SMC express Type I, II and III receptors. The Type II receptor is strikingly decreased in lesion cells, with little change in the Type I or III receptors. RT-PCR confirmed that the Type II TGF-beta1 receptor mRNA is reduced in lesion cells. Subsequent analysis of human lesion vs normal tissues confirmed that the Type I receptor was consistently present in the lesion, while the Type II receptor was much more variable, and commonly absent in both coronary artery and carotid artery lesions. Transfection of the Type II receptor into lesion cells partially restores the growth inhibitory response to TGF-beta1, implying that signaling remains intact. A subset of patients, and cells derived from their lesions, exhibit acquired mutations in the Type II receptor that would explain their resistance, though the majority of cells are resistant without obvious mutational defects. Thus, it is currently being tested whether transcriptional defects or abnormalities in receptor processing may explain the low levels of the Type II receptor. Because TGF-beta1 is overexpressed in fibroproliferative vascular lesions, receptor-negative cells would be allowed to grow in a slow, but uncontrolled fashion, while overproducing extracellular matrix components.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1359-6101
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
103-14
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10708958-Activin Receptors, Type I, pubmed-meshheading:10708958-Aging, pubmed-meshheading:10708958-Angioplasty, pubmed-meshheading:10708958-Animals, pubmed-meshheading:10708958-Arteriosclerosis, pubmed-meshheading:10708958-Constriction, Pathologic, pubmed-meshheading:10708958-Cytoskeleton, pubmed-meshheading:10708958-Endothelium, Vascular, pubmed-meshheading:10708958-Extracellular Matrix, pubmed-meshheading:10708958-Humans, pubmed-meshheading:10708958-Mutation, pubmed-meshheading:10708958-Protein-Serine-Threonine Kinases, pubmed-meshheading:10708958-RNA, Messenger, pubmed-meshheading:10708958-Receptors, Transforming Growth Factor beta, pubmed-meshheading:10708958-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10708958-Transforming Growth Factor beta
pubmed:articleTitle
TGF-betas and TGF-beta receptors in atherosclerosis.
pubmed:affiliation
Weill Medical College of Cornell University, Department of Medicine, Division of Hematology/Oncology, New York, NY 10021, USA. tamccaf@med.cornell.edu
pubmed:publicationType
Journal Article, Review