Linked Life Data

17272808

Source:http://linkedlifedata.com/resource/pubmed/id/17272808

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-3-2
pubmed:abstractText
Steady laminar flow in the straight parts of the arterial tree is atheroprotective, whereas disturbed flow with oscillation in branch points and the aortic root are athero-prone, in part, because of the distinct roles of the flow patterns in regulating the cell cycle of vascular endothelial cells (ECs). To elucidate the molecular basis underlying the endothelial cell cycle regulated by distinct flow patterns, we conducted flow-channel experiments to investigate the effects of laminar versus oscillatory flows on activation of AMP-activated protein kinase (AMPK) and Akt in ECs. Laminar flow caused a transient activation of both AMPK and Akt, but oscillatory flow activated only Akt, with AMPK being maintained at its basal level. Constitutively active and dominant-negative mutants of AMPK and Akt were used to elucidate further the positive effect of Akt and negative role of AMPK in mediating mTOR (mammalian target of rapamycin) and its target p70S6 kinase (S6K) in response to laminar and oscillatory flows. Measurements of phosphorylation of mTOR Ser2448 and S6K Thr389 showed that AMPK, by counteracting Akt under laminar flow, resulted in a transient activation of S6K. Under oscillatory flow, because of the lack of AMPK activation to effect negative regulation, S6K was activated in a sustained manner. As a functional consequence, AMPK activation attenuated cell cycle progression in response to both laminar and oscillatory flows. In contrast, AMPK inhibition promoted EC cycle progression by decreasing the cell population in the G(0)/G(1) phase and increasing it in the S+G(2)/M phase. In vivo, phosphorylation of the promitotic S6K in mouse thoracic aorta was much less than that in mouse aortic root. In contrast, AMPK phosphorylation was higher in the thoracic aorta. These results provide a molecular mechanism by which laminar versus oscillatory flow regulates the endothelial cell cycle.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
564-71
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17272808-AMP-Activated Protein Kinases, pubmed-meshheading:17272808-Animals, pubmed-meshheading:17272808-Blood Flow Velocity, pubmed-meshheading:17272808-Cattle, pubmed-meshheading:17272808-Cell Culture Techniques, pubmed-meshheading:17272808-Cell Cycle, pubmed-meshheading:17272808-Cells, Cultured, pubmed-meshheading:17272808-Endothelial Cells, pubmed-meshheading:17272808-Endothelium, Vascular, pubmed-meshheading:17272808-Male, pubmed-meshheading:17272808-Mice, pubmed-meshheading:17272808-Mice, Inbred C57BL, pubmed-meshheading:17272808-Multienzyme Complexes, pubmed-meshheading:17272808-Protein-Serine-Threonine Kinases, pubmed-meshheading:17272808-Proto-Oncogene Proteins c-akt, pubmed-meshheading:17272808-Signal Transduction, pubmed-meshheading:17272808-Stress, Mechanical
pubmed:year
2007
pubmed:articleTitle
Regulation of endothelial cell cycle by laminar versus oscillatory flow: distinct modes of interactions of AMP-activated protein kinase and Akt pathways.
pubmed:affiliation
Division of Biomedical Sciences, University of California, Riverside, CA 92521-0121, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural