Linked Life Data

10845864

Source:http://linkedlifedata.com/resource/pubmed/id/10845864

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-6-22
pubmed:abstractText
We previously demonstrated that homogeneous cultures of vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats produce angiotensin II (Ang II) in response to increases in the levels of angiotensinogen, cathepsin D, and angiotensin-converting enzyme (ACE). The change of VSMCs from the contractile to the synthetic phenotype increased the amount of synthetic organelles, resulting in the production of proteases and growth factors. To evaluate the contribution of the synthetic phenotype to the generation of Ang II, we examined the effect of fibronectin (FN), which reportedly induces the synthetic phenotype, on the Ang II-generating system in VSMCs. Cultured VSMCs from Wistar-Kyoto rats were incubated with an active fragment of FN, Arg-Gly-Asp-Ser, for 24, 48, or 72 hours after synchronization of the cell cycle with 0. 2% calf serum for 48 hours. Immunofluorescence and protein levels of alpha-smooth muscle (SM) actin and expression of SM22alpha mRNA, apparent in the contractile phenotype, were suppressed by FN, whereas expression of matrix Gla mRNA and osteopontin mRNA and protein, apparent in the synthetic phenotype, was increased. FN (1 to 1000 microg/mL) dose-dependently increased DNA synthesis in the VSMCs, which was inhibited by the Ang II type 1 receptor antagonist CV-11974. Ang II-like immunoreactivity as determined by radioimmunoassay was significantly increased in conditioned medium from the VSMCs. In addition, mRNA for the Ang II-generating proteases cathepsin D and ACE was increased by FN. Expression of transforming growth factor-beta1, platelet-derived growth factor A-chain, and basic fibroblast growth factor mRNAs was also increased by FN. These results indicate that the changes accompanying the alteration to the synthetic phenotype in homogeneous cultures of VSMCs increase expression of proteases such as cathepsin D and ACE, which then produce Ang II, and that these changes increase expression of growth factors that then induce growth of VSMCs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1079-5642
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1500-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10845864-Angiotensin II, pubmed-meshheading:10845864-Animals, pubmed-meshheading:10845864-Aorta, pubmed-meshheading:10845864-Blotting, Western, pubmed-meshheading:10845864-Cathepsin D, pubmed-meshheading:10845864-Cell Division, pubmed-meshheading:10845864-Cells, Cultured, pubmed-meshheading:10845864-Fibroblast Growth Factor 2, pubmed-meshheading:10845864-Fibronectins, pubmed-meshheading:10845864-Gene Expression, pubmed-meshheading:10845864-Kinetics, pubmed-meshheading:10845864-Male, pubmed-meshheading:10845864-Muscle, Smooth, Vascular, pubmed-meshheading:10845864-Peptide Fragments, pubmed-meshheading:10845864-Peptidyl-Dipeptidase A, pubmed-meshheading:10845864-Phenotype, pubmed-meshheading:10845864-Rats, pubmed-meshheading:10845864-Rats, Inbred WKY, pubmed-meshheading:10845864-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10845864-Transforming Growth Factor beta
pubmed:year
2000
pubmed:articleTitle
Phenotypic modulation by fibronectin enhances the angiotensin II-generating system in cultured vascular smooth muscle cells.
pubmed:affiliation
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't