Linked Life Data

17210832

Source:http://linkedlifedata.com/resource/pubmed/id/17210832

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-2-16
pubmed:abstractText
The hypertrophic response of the heart has been recognized recently as the net result of activation of prohypertrophic and antihypertrophic pathways. Here we report the involvement of the Wnt/Frizzled pathway in the onset of cardiac hypertrophy development. Stimulation of the Wnt/Frizzled pathway activates the disheveled (Dvl) protein. Disheveled subsequently can inhibit glycogen synthase kinase-3beta, a protein with potent antihypertrophic actions through diverse molecular mechanisms. In the Wnt/Frizzled pathway, inhibition of glycogen synthase kinase-3beta leads to an increased amount of beta-catenin, which can act as a transcription factor for several hypertrophy-associated target genes. In this study we subjected mice lacking the Dvl-1 gene and their wild-type littermates to thoracic aortic constriction for 7, 14, and 35 days. In mice lacking the Dvl-1 gene, 7 days of pressure overload-induced increases in left ventricular posterior wall thickness and expression of atrial natriuretic factor and brain natriuretic protein were attenuated compared with their wild-type littermates. Beta-catenin protein amount was reduced in the group lacking the Dvl-1 gene, and an increased glycogen synthase kinase-3beta activity was observed. Moreover, the increase in the amount of Ser(473)-phosphorylated Akt, a stimulator of cardiac hypertrophy, was lower in the group lacking the Dvl-1 gene. In conclusion, we have demonstrated that interruption of Wnt signaling in the mice lacking the Dvl-1 gene attenuates the onset of pressure overload-induced cardiac hypertrophy through mechanisms involving glycogen synthase kinase-3beta and Akt. Therefore, the Wnt/Frizzled pathway may provide novel therapeutic targets for antihypertrophic therapy.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
473-80
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:17210832-Adaptor Proteins, Signal Transducing, pubmed-meshheading:17210832-Animals, pubmed-meshheading:17210832-Aortic Coarctation, pubmed-meshheading:17210832-Cardiomegaly, pubmed-meshheading:17210832-Disease Models, Animal, pubmed-meshheading:17210832-Female, pubmed-meshheading:17210832-Frizzled Receptors, pubmed-meshheading:17210832-Glycogen Synthase Kinase 3, pubmed-meshheading:17210832-Hypertension, pubmed-meshheading:17210832-Male, pubmed-meshheading:17210832-Mice, pubmed-meshheading:17210832-Mice, Knockout, pubmed-meshheading:17210832-Natriuretic Peptides, pubmed-meshheading:17210832-Phosphoproteins, pubmed-meshheading:17210832-Proto-Oncogene Proteins c-akt, pubmed-meshheading:17210832-Signal Transduction, pubmed-meshheading:17210832-Wnt Proteins, pubmed-meshheading:17210832-beta Catenin
pubmed:year
2007
pubmed:articleTitle
Interruption of Wnt signaling attenuates the onset of pressure overload-induced cardiac hypertrophy.
pubmed:affiliation
Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Evaluation Studies