Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-4-21
pubmed:abstractText
Proliferation of smooth muscle cells (SMCs) is the key event in the pathogenesis of intimal hyperplasia (IH) leading to coronary artery bypass graft (CABG) occlusion. The saphenous vein (SV) conduits are often affected by IH, while the internal mammary artery (IMA) conduits remain remarkably patent. SMC proliferation is mediated by the cell cycle, under the control of cyclin-dependent kinases (cdks), cdk-inhibitors and the retinoblastoma protein (Rb). Early passage of the SMCs through the cell cycle involves crossing the non-reversible G(1) checkpoint, the restriction (R) point. In this study, we investigated the effect of mitogenic insulin-like growth factor (IGF)-1 stimulation on the R-point and its relationship with the phosphorylation of Rb protein and the cdk inhibitors p21 and p27 in SV and IMA SMCs. We observed no change in the R-point following IGF-1 activation in either SV or IMA SMCs. However, Rb-phosphorylation occurred much earlier and was quantitatively greater in SV SMCs than IMA. Overexpression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in SV SMCs followed by IGF-1 activation significantly decreased the expression of cyclin E and pRb and induced p27 expression in SV SMCs, while, pRb levels were markedly decreased and p27 levels were significantly increased in IMA SMCs. Silencing the PTEN gene by siRNA transfection of IMA SMCs significantly induced the expression of pRb and inhibited p27 expression, while, the expression levels of cyclin E, pRb, p21 and p27 were unaffected by the silencing of PTEN in SV SMCs. These results demonstrate that the PTEN plays a critical role in regulating cell cycle entry. Therefore, overexpression of PTEN possibly by means of gene therapy could be a viable option in regulating the cell cycle in SV SMCs in the treatment of vein graft disease.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-10082542, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-10331086, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-10920930, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-11549719, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-12057987, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-12411952, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-14559444, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-15534858, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-16098957, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-16158973, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-16289477, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-16969133, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-17624368, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-18405916, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-4524638, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-8212198, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-8427857, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-8755575, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-8939849, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-9062614, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-9442875, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-9665064, http://linkedlifedata.com/resource/pubmed/commentcorrection/18544045-9823298
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1582-4934
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
547-54
pubmed:dateRevised
2011-11-8
pubmed:meshHeading
pubmed-meshheading:18544045-Aged, pubmed-meshheading:18544045-Cell Cycle, pubmed-meshheading:18544045-Cell Proliferation, pubmed-meshheading:18544045-Coronary Artery Bypass, pubmed-meshheading:18544045-Cyclin E, pubmed-meshheading:18544045-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:18544045-Cyclin-Dependent Kinase Inhibitor p27, pubmed-meshheading:18544045-Gene Silencing, pubmed-meshheading:18544045-Humans, pubmed-meshheading:18544045-Insulin-Like Growth Factor I, pubmed-meshheading:18544045-Mammary Arteries, pubmed-meshheading:18544045-Middle Aged, pubmed-meshheading:18544045-Myocytes, Smooth Muscle, pubmed-meshheading:18544045-PTEN Phosphohydrolase, pubmed-meshheading:18544045-Phosphorylation, pubmed-meshheading:18544045-Retinoblastoma Protein, pubmed-meshheading:18544045-Saphenous Vein, pubmed-meshheading:18544045-Transfection
pubmed:year
2009
pubmed:articleTitle
Regulation of cell cycle entry by PTEN in smooth muscle cell proliferation of human coronary artery bypass conduits.
pubmed:affiliation
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural