Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-4-21
pubmed:abstractText
Angiotensin-II (AII), the dominant effector of the renin-angiotensin system, is involved in the pathogenesis of cardiovascular diseases, such as atherosclerosis. Upregulation of the adhesion molecules VCAM-1, ICAM-1, and E-selectin in endothelial cells by inflammatory cytokines through nuclear factor kappa B (NFkappaB) activation is implicated in formation and progression of atherosclerotic plaque. Here we show that AII induces NFkappaB-dependent transcription in primary endothelial cell lines, leading to the upregulation of ICAM-1 and VCAM-1 expression. NFkappaB activation by AII is mediated by the NFkappaB-inducing kinase (NIK), a common mediator of NFkappaB activation by inflammatory cytokines, such as TNF-alpha. However, NFkappaB stimulation by AII differs from that of TNF-alpha since a TNF-receptor associated factor 2 (TRAF-2) dominant negative mutant does not prevent AII-mediated NFkappaB activation. In analogy with TNF-alpha-dependent activation of NFkappaB, treatment with either the anti-oxidant N-acetyl cysteine (NAC) or the cyclooxygenase (COX) inhibitor acetyl salicylic acid (aspirin), but not indometacin, prevents the induction of NFkappaB-dependent transcription by AII. Thus, production of reactive oxygen species, aspirin (asp)-sensitive enzymes of the arachidonate metabolism, and NIK are common transducers of AII- and TNF-dependent pathways to NFkappaB. AII also activates the inflammatory p38 kinase in endothelial cells, an effect inhibited by exposure to either NAC or asp. Pharmacological interference of the p38 pathway, with the inhibitor SB 202190, prevented AII-mediated activation of the NFkappaB target V-CAM, without affecting degradation of IkappaBalpha. These results support a pro-inflammatory effect of the vasoactive peptide AII in endothelial cells, through at least two pathways-NFkappaB and p38-both of which are sensitive to asp and antioxidants.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II, http://linkedlifedata.com/resource/pubmed/chemical/Aspirin, http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B kinase, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species, http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 2, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1, http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9541
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
195
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
402-10
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:12704649-Angiotensin II, pubmed-meshheading:12704649-Aspirin, pubmed-meshheading:12704649-Cells, Cultured, pubmed-meshheading:12704649-Endothelium, Vascular, pubmed-meshheading:12704649-Humans, pubmed-meshheading:12704649-Intercellular Adhesion Molecule-1, pubmed-meshheading:12704649-Mitogen-Activated Protein Kinases, pubmed-meshheading:12704649-NF-kappa B, pubmed-meshheading:12704649-Protein-Serine-Threonine Kinases, pubmed-meshheading:12704649-Proteins, pubmed-meshheading:12704649-Reactive Oxygen Species, pubmed-meshheading:12704649-Signal Transduction, pubmed-meshheading:12704649-TNF Receptor-Associated Factor 2, pubmed-meshheading:12704649-Transcriptional Activation, pubmed-meshheading:12704649-Tumor Necrosis Factor-alpha, pubmed-meshheading:12704649-Vascular Cell Adhesion Molecule-1, pubmed-meshheading:12704649-p38 Mitogen-Activated Protein Kinases
pubmed:year
2003
pubmed:articleTitle
Endothelial activation by angiotensin II through NFkappaB and p38 pathways: Involvement of NFkappaB-inducible kinase (NIK), free oxygen radicals, and selective inhibition by aspirin.
pubmed:affiliation
Laboratory of Gene Expression, Fondazione Andrea Cesalpino, Universita' degli Studi di Roma La Sapienza, Viale del Policlinico 155, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't