Linked Life Data

19664058

Source:http://linkedlifedata.com/resource/pubmed/id/19664058

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2009-8-21
pubmed:abstractText
Factor VII-activating protease (FSAP) circulates as an inactive zymogen in the plasma. FSAP also regulates fibrinolysis by activating pro-urokinase or cellular activation via cleavage of platelet-derived growth factor BB (PDGF-BB). As the Marburg I polymorphism of FSAP, with reduced enzymatic activity, is a risk factor for atherosclerosis and liver fibrosis, the regulation of FSAP activity is of major importance. FSAP is activated by an auto-catalytic mechanism, which is amplified by heparin. To further investigate the structural requirements of polyanions for controlling FSAP activity, we performed binding, activation and inhibition studies using heparin and derivatives with altered size and charge, as well as other glycosaminoglycans. Heparin was effective in binding to and activating FSAP in a size- and charge density-dependent manner. Polyphosphate was more potent than heparin with regard to its interactions with FSAP. Heparin was also an effective co-factor for inhibition of FSAP by plasminogen activator inhibitor 1 (PAI-1) and antithrombin, whereas polyphosphate served as co-factor for the inhibition of FSAP by PAI-1 only. For FSAP-mediated inhibition of PDGF-BB-induced vascular smooth muscle cell proliferation, heparin as well as a polyphosphate served as efficient co-factors. Native mast cell-derived heparin exhibited identical properties to those of unfractionated heparin. Despite the strong effects of synthetic polyphosphate, the platelet-derived material was a weak activator of FSAP. Hence, negatively charged polymers with a high charge-to-size ratio are responsible for the activation of FSAP, and also act as co-factors for its inhibition by serine protease inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1742-4658
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4828-39
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
High negative charge-to-size ratio in polyphosphates and heparin regulates factor VII-activating protease.
pubmed:affiliation
Institute for Biochemistry, Justus-Liebig-University, Giessen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't