Document Detail


Factor VII-activating protease (FSAP) inhibits growth factor-mediated cell proliferation and migration of vascular smooth muscle cells.
MedLine Citation:
PMID:  14977886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The factor VII activating protease (FSAP) is a serine-protease present in human plasma that serves to activate single-chain plasminogen activators, as well as coagulation factor VII. FSAP was localized within atherosclerotic lesions, and a genetic polymorphism in FSAP is associated with carotid stenosis. Hence, this study was conducted to gain broader insights into the cellular effects of FSAP on vascular smooth muscle cells (VSMC). DNA synthesis and cell proliferation assays revealed an inhibitory action of FSAP on platelet-derived growth factor BB (PDGF-BB)-mediated proliferation of VSMC. FSAP also inhibited PDGF-BB-induced migration of VSMC. These cellular effects of FSAP could be neutralized by an anti-FSAP mAb as well as by protease inhibitors such as aprotinin or a chloromethylketone inhibitor. Moreover, unfractionated heparin promoted the antiproliferative effect of FSAP on VSMC and was essential for the inhibition of VSMC migration. FSAP inhibited PDGF-BB binding to human VSMC and concomitantly blocked PDGF-BB-dependent phosphorylation of mitogen activated protein kinase p42/p44 and tyrosine phosphorylation of other proteins. These results unravel a new function of FSAP as an inhibitor of the proatherogenic phenotype of vascular smooth muscle.
Authors:
Christian Kannemeier; Nadia Al-Fakhri; Klaus T Preissner; Sandip M Kanse
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Publication Detail:
Type:  Journal Article     Date:  2004-02-20
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  18     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-31     Completed Date:  2004-07-15     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  728-30     Citation Subset:  IM    
Affiliation:
Institute for Biochemistry, Justus-Liebig-University Giessen, Giessen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Arteriosclerosis / metabolism,  pathology
Carotid Arteries / chemistry
Cell Division / drug effects
Cell Movement / drug effects
DNA / biosynthesis
Humans
Models, Biological
Muscle, Smooth, Vascular / cytology,  drug effects,  physiology*
Phosphorylation
Platelet-Derived Growth Factor / antagonists & inhibitors*,  metabolism
Serine Endopeptidases / analysis,  metabolism,  pharmacology*
Signal Transduction
Chemical
Reg. No./Substance:
0/Platelet-Derived Growth Factor; 0/platelet-derived growth factor BB; 9007-49-2/DNA; EC 3.4.21.-/HABP2 protein, human; EC 3.4.21.-/Serine Endopeptidases

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