Linked Life Data

21075101

Source:http://linkedlifedata.com/resource/pubmed/id/21075101

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-3
pubmed:abstractText
Apoptosis of vascular smooth muscle cells (SMCs) is controlled by a balance between the effect of growth factors and cytokines, and is involved in plaque instability in advanced atherosclerotic lesions. Recently, we reported high levels of atheroma-associated cytokines, including tumor necrosis factor-? (TNF-?), in carotid plaques of symptomatic patients. These cytokines induce apoptosis of vascular SMCs, and thus could be responsible for plaque rupture, a clinically devastating event. In this study, we examined the effect of TNF-? on the cell cycle inhibitor p27(kip) and apoptosis of SMCs in human carotid plaques, and the underlying mechanism. Both Forkhead box subclass o1 (FoxO1) and p27(kip) were more strongly expressed in symptomatic than asymptomatic atherosclerotic plaques. TNF-? significantly induced the expression of FoxO1 in asymptomatic plaque SMCs in a dose- and time-dependent manner via JNK signaling pathway. TNF-? also induced phosphorylation of FoxO1, resulting in its cytoplasmic translocation/nuclear exclusion of transcription factors. The effect of TNF-? was blocked by the PI3K inhibitor, LY294002. Meanwhile, TNF-? not only induced the p27(kip) expression and cell cycle arrest in the G(0)-G(1) phase, but also enhanced caspase-3 activity and induced apoptosis in SMCs of asymptomatic plaques. However, the potential effect of TNF-? on the cell cycle inhibitor p27(kip) and apoptosis of SMCs was inhibited by siRNA against FoxO1 in asymptomatic patients. These data suggest the involvement of FoxO1 transcription factor in TNF-?-induced expression of a cell cycle regulatory protein and apoptosis of SMCs, thus regulating the stability of atherosclerotic plaques with carotid stenosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1096-0945
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Tumor necrosis factor-? regulates p27 kip expression and apoptosis in smooth muscle cells of human carotid plaques via forkhead transcription factor O1.
pubmed:affiliation
Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE 68178, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural