Linked Life Data

14605018

Source:http://linkedlifedata.com/resource/pubmed/id/14605018

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2003-12-3
pubmed:abstractText
Constitutive activation of serine/threonine kinase Akt causes uncontrolled cell-cycle progression in different cell types and in malignancy. To investigate how Akt activation modulates cell-cycle progression in vascular smooth muscle cells (SMCs) in vitro and in the intact animal, we inhibited Akt-dependent signaling by adenovirus-mediated transfection of a dominant-negative Akt mutant (AA-Akt). We observed reduced proliferation rate (P<0.01), DNA synthesis (P<0.01), and a significant arrest in G1/S exit (P<0.01) both in vitro in response to serum stimulation and in vivo after vascular injury. In vivo transfection of the balloon-injured vessel with AA-Akt reduced SMC proliferation, resulting in decreased neointima compared with control virus (P<0.01). These effects were at least in part modulated, both in vitro and in vivo, by increased p21Cip1 expression, as demonstrated by lack of effect of AA-Akt on cell proliferation in p21-/- mouse SMCs. In conclusion, this study demonstrates that Akt-dependent signaling enhances cell-cycle progression of nontransformed SMCs in vitro and in response to vascular injury in the intact animal. These results suggest a role for Akt signaling in modulating the response of normal tissues to stress and the response of the arterial wall to acute and possibly repetitive injuries that ultimately contribute to restenosis and atherosclerosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1059-65
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14605018-Adenoviridae, pubmed-meshheading:14605018-Angioplasty, Balloon, pubmed-meshheading:14605018-Animals, pubmed-meshheading:14605018-Blood Proteins, pubmed-meshheading:14605018-Carotid Stenosis, pubmed-meshheading:14605018-Cell Division, pubmed-meshheading:14605018-Cells, Cultured, pubmed-meshheading:14605018-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:14605018-Cyclins, pubmed-meshheading:14605018-Disease Models, Animal, pubmed-meshheading:14605018-G1 Phase, pubmed-meshheading:14605018-Gene Therapy, pubmed-meshheading:14605018-Genes, Dominant, pubmed-meshheading:14605018-Graft Occlusion, Vascular, pubmed-meshheading:14605018-Male, pubmed-meshheading:14605018-Mice, pubmed-meshheading:14605018-Mice, Knockout, pubmed-meshheading:14605018-Muscle, Smooth, Vascular, pubmed-meshheading:14605018-Protein-Serine-Threonine Kinases, pubmed-meshheading:14605018-Proto-Oncogene Proteins, pubmed-meshheading:14605018-Proto-Oncogene Proteins c-akt, pubmed-meshheading:14605018-Rats, pubmed-meshheading:14605018-Rats, Sprague-Dawley, pubmed-meshheading:14605018-Ribosomal Protein S6 Kinases, 70-kDa, pubmed-meshheading:14605018-S Phase, pubmed-meshheading:14605018-Signal Transduction
pubmed:year
2003
pubmed:articleTitle
Akt controls vascular smooth muscle cell proliferation in vitro and in vivo by delaying G1/S exit.
pubmed:affiliation
Cardiovascular Research Institute, Washington Hospital Center, 110 Irving St NW, 4B-1, Washington, DC 20010, USA. geko50@katamail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't