Linked Life Data

20960543

Source:http://linkedlifedata.com/resource/pubmed/id/20960543

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-11-24
pubmed:abstractText
Disease or malformation of heart valves is one of the leading causes of morbidity and mortality in both children and adults. These congenital anomalies can remain undetected until cardiac function is compromised, making it important to understand the underlying nature of these disorders. Here we show that ephrin-A1, a ligand for class A Eph receptor tyrosine kinases, regulates cardiac valve formation. Exogenous ephrin-A1-Fc or overexpression of ephrin-A1 in the heart inhibits epithelial-to-mesenchymal transformation (EMT) in chick atrioventricular cushion explants. In contrast, overexpression of wild-type EphA3 receptor promotes EMT via a kinase-dependent mechanism. To analyze ephrin-A1 in vivo, we generated an ephrin-A1 knockout mouse through gene targeting. Ephrin-A1 null animals are viable but exhibit impaired cardiac function. Loss of ephrin-A1 results in thickened aortic and mitral valves in newborn and adult animals. Analysis of early embryonic hearts revealed increased cellularity in outflow tract endocardial cushions and elevated mesenchymal marker expression, suggesting that excessive numbers of cells undergo EMT. Taken together, these data indicate that ephrin-A1 regulates cardiac valve development, making ephrin-A1-deficient mice a novel model for congenital heart defects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1097-0177
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
239
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3226-34
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Regulation of heart valve morphogenesis by Eph receptor ligand, ephrin-A1.
pubmed:affiliation
Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2363, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural