Linked Life Data

11049984

Source:http://linkedlifedata.com/resource/pubmed/id/11049984

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-12-11
pubmed:abstractText
Tissue factor, which is expressed in vascular lesions, increases thrombin production, blood coagulation, and smooth muscle cell proliferation. We demonstrate that oxidized low-density lipoprotein (LDL) induces surface tissue factor pathway activity (ie, activity of the tissue factor:factor VIIa complex) on human and rat smooth muscle cells. Tissue factor messenger RNA (mRNA) was induced by oxidized LDL or native LDL; however, native LDL did not markedly increase tissue factor activity. We hypothesized that oxidized LDL mediated the activation of the tissue factor pathway via an oxidant-dependent mechanism, because antioxidants blocked the enhanced tissue factor pathway activity by oxidized LDL, but not the increased mRNA or protein induction. We separated total lipid extracts of oxidized LDL using high-performance liquid chromatography (HPLC). This yielded 2 major peaks that induced tissue factor activity. Of the known oxysterols contained in the first peak, 7alpha- or 7beta-hydroxy or 7-ketocholesterol had no effect on tissue factor pathway activity; however, 7beta-hydroperoxycholesterol increased tissue factor pathway activity without induction of tissue factor mRNA. Tertiary butyl hydroperoxide also increased tissue factor pathway activity, suggesting that lipid hydroperoxides, some of which exist in atherosclerotic lesions, activate the tissue factor pathway. We speculate that thrombin production could be elevated via a mechanism involving peroxidation of cellular lipids, contributing to arterial thrombosis after plaque rupture. Our data suggest a mechanism by which antioxidants may offer a clinical benefit in acute coronary syndrome and restenosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3056-63
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11049984-1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt, pubmed-meshheading:11049984-Animals, pubmed-meshheading:11049984-Antioxidants, pubmed-meshheading:11049984-Aorta, pubmed-meshheading:11049984-Azoles, pubmed-meshheading:11049984-Cells, Cultured, pubmed-meshheading:11049984-Deferoxamine, pubmed-meshheading:11049984-Humans, pubmed-meshheading:11049984-Kinetics, pubmed-meshheading:11049984-Lipid Peroxidation, pubmed-meshheading:11049984-Lipoproteins, LDL, pubmed-meshheading:11049984-Muscle, Smooth, Vascular, pubmed-meshheading:11049984-Organoselenium Compounds, pubmed-meshheading:11049984-Rats, pubmed-meshheading:11049984-Rats, Sprague-Dawley, pubmed-meshheading:11049984-Thromboplastin, pubmed-meshheading:11049984-Tin Compounds, pubmed-meshheading:11049984-Transcription, Genetic
pubmed:year
2000
pubmed:articleTitle
Smooth muscle cell surface tissue factor pathway activation by oxidized low-density lipoprotein requires cellular lipid peroxidation.
pubmed:affiliation
Departments of Cardiology, Cell Biology, and Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't