Linked Life Data

8696947

Source:http://linkedlifedata.com/resource/pubmed/id/8696947

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1996-9-5
pubmed:abstractText
Basic fibroblast growth factor (bFGF), a potent mitogen for arterial smooth muscle cells (SMCs), plays a pivotal role in the pathogenesis of arteriosclerosis and restenosis. Heparin in nanogram quantities may promote or even be required for binding of bFGF to its cognate receptor. Conversely, heparin in microgram doses is a strong inhibitor of arterial SMC replication in vitro and in vivo. Bovine coronary SMCs (cSMCs) express bFGF, bFGF receptor (FGF-R1), and cell membrane-integrated proteoheparan sulfate (HSPG). These three molecules are known to form a trimolecular complex that promotes signal transduction and mitogenesis. The bFGF synthesized by cSMCs is distributed to an intracellular and a pericellular compartment. Resting cultured cells retain about 80% of their bFGF intracellularly; 20% is found in the pericellular region. During proliferation, 70% to 80% of total bFGF is expressed in the pericellular compartment. Trypsinization generates soluble forms of the complex of bFGF with the ectodomains of the bFGF receptor and cell membrane-integrated HSPG in the pericellular compartment, thus allowing quantification of pericellular bFGF by a highly specific enzyme immunoassay. Standard heparin inhibits the proliferation of cSMCs by up to 80% in a concentration range between 10 and 100 micrograms/mL medium in a dose-dependent manner but increases the protein content of cSMCs compared with proliferating control cells. The heparin-induced increase in cellular protein content includes a 60% to 100% increase in the expression of pericellular bFGF, FGF-R1, and cell membrane-integrated HSPG. Thus, under heparin treatment, the heparan sulfate side chains of cell membrane-integrated HSPG incorporate more [35S]sulfate, and the proportion of [35S]heparan sulfate among total glycosaminoglycans increases from 36% to 52%. Fluorescence-activated cell sorting analysis and [3H]thymidine incorporation experiments provide evidence for multiple effects of heparin, including blocks at early and late checkpoints of the cell cycle in heparin-treated cells. These results indicate that heparin, despite its anti-proliferative potency, stimulates the expression of all components of the bFGF system even in coronary SMCs in which growth is inhibited.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1079-5642
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1063-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8696947-Animals, pubmed-meshheading:8696947-Cattle, pubmed-meshheading:8696947-Cell Cycle, pubmed-meshheading:8696947-Cell Division, pubmed-meshheading:8696947-Cells, Cultured, pubmed-meshheading:8696947-Fibroblast Growth Factor 2, pubmed-meshheading:8696947-Gene Expression Regulation, pubmed-meshheading:8696947-Growth Inhibitors, pubmed-meshheading:8696947-Growth Substances, pubmed-meshheading:8696947-Heparan Sulfate Proteoglycans, pubmed-meshheading:8696947-Heparin, pubmed-meshheading:8696947-Heparitin Sulfate, pubmed-meshheading:8696947-Muscle, Smooth, Vascular, pubmed-meshheading:8696947-Proteoglycans, pubmed-meshheading:8696947-Receptor, Fibroblast Growth Factor, Type 1, pubmed-meshheading:8696947-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:8696947-Receptors, Fibroblast Growth Factor
pubmed:year
1996
pubmed:articleTitle
Heparin-induced overexpression of basic fibroblast growth factor, basic fibroblast growth factor receptor, and cell-associated proteoheparan sulfate in cultured coronary smooth muscle cells.
pubmed:affiliation
Institute for Arteriosclerosis Research, Division of Molecular Cardiology, Hospital of the University of Münster, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't