Linked Life Data

15384983

Source:http://linkedlifedata.com/resource/pubmed/id/15384983

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-9-23
pubmed:abstractText
Modified lipoproteins have been suggested to modulate endothelial expression of plasminogen activator inhibitor-1 (PAI-1). As oxidized high-density lipoprotein (Ox-HDL) has been found in atheromatous plaques and receptors for modified HDL are present on endothelial cells, we investigated the role of Ox-HDL3 on the expression of PAI-1. Ox-HDL3 but not native HDL3, increased PAI-1 mRNA expression in endothelial cells. Furthermore, PAI-1 antigen expression and activity increased in the supernatant of cells incubated with Ox-HDL3. The intracellular pathways involved in this effect were investigated. Ox-HDL3 activated both extracellular signal-regulated kinases (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK). Moreover, incubation with specific inhibitors of these kinases showed that p38MAPK was mainly involved in the Ox-HDL3-dependent PAI-1 induction. Transient transfection experiments suggested that none of the response elements in the proximal promoter (-804 to 17) were involved in Ox-HDL3-mediated PAI-1 expression. mRNA stability experiments showed that Ox-HDL3 increased the PAI-1 mRNA half-life. In summary, Ox-HDL3 induced PAI-1 mRNA expression and antigen release through a molecular mechanism involving MAPK activation and mRNA stabilization. Thus, oxidative modification converts HDL to a prothrombotic lipoprotein species.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0007-1048
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Blackwell Publishing Ltd
pubmed:issnType
Print
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
97-104
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Oxidised-HDL3 induces the expression of PAI-1 in human endothelial cells. Role of p38MAPK activation and mRNA stabilization.
pubmed:affiliation
Department of Pharmacological Sciences, University of Milan, Milan, Italy. danilo.norata@unimi.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't