Document Detail

Tetralogy of fallot and alterations in vascular endothelial growth factor-A signaling and notch signaling in mouse embryos solely expressing the VEGF120 isoform.
MedLine Citation:
PMID:  17332426     Owner:  NLM     Status:  MEDLINE    
The importance of vascular endothelial growth factor-A (VEGF) and subsequent Notch signaling in cardiac outflow tract development is generally recognized. Although genetic heterogeneity and mutations of these genes in both humans and mouse models relate to a high susceptibility to develop outflow tract malformations such as tetralogy of Fallot and peripheral pulmonary stenosis, no etiology has been proposed so far. Using immunohistochemistry, in situ hybridization, and quantitative RT-PCR on embryonic hearts, we have shown spatiotemporal increase and abnormal patterning of Vegf/VEGF/(phosphorylated) VEGFR-2, (cleaved) Notch1, and Jagged2 in the outflow tract of Vegf120/120 mouse embryos. This coincides with hyperplasia of specifically the outflow tract cushions and a high degree of subpulmonary myocardial apoptosis that, in later stages, manifest as pulmonary stenosis and ventricular septal defects. We postulate that increase of VEGF and Notch signaling during right ventricular outflow tract development can lead to abnormal development of both cushion and myocardial structures. Defective right ventricular outflow tract development as presented provides new insight in the etiology of tetralogy of Fallot.
Nynke M S van den Akker; Daniël G M Molin; Patricia P W M Peters; Saskia Maas; Lambertus J Wisse; Ronald van Brempt; Conny J van Munsteren; Margot M Bartelings; Robert E Poelmann; Peter Carmeliet; Adriana C Gittenberger-de Groot
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-03-01
Journal Detail:
Title:  Circulation research     Volume:  100     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-30     Completed Date:  2007-04-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  842-9     Citation Subset:  IM    
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
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MeSH Terms
Aorta, Thoracic / abnormalities,  pathology
Disease Models, Animal
Embryo, Mammalian / abnormalities*,  metabolism,  pathology
Gene Expression Regulation, Developmental
Heart Ventricles / abnormalities,  pathology
In Situ Hybridization
Membrane Proteins / metabolism
Mice, Mutant Strains
Myocardium / metabolism*,  pathology
Protein Isoforms / genetics,  metabolism
RNA, Messenger / metabolism
Receptor, Notch1 / genetics*,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / genetics*
Tetralogy of Fallot / genetics*
Vascular Endothelial Growth Factor A / genetics*,  metabolism
Vascular Endothelial Growth Factor Receptor-2 / metabolism
Reg. No./Substance:
0/Jag2 protein, mouse; 0/Membrane Proteins; 0/Notch1 protein, mouse; 0/Protein Isoforms; 0/RNA, Messenger; 0/Receptor, Notch1; 0/Vascular Endothelial Growth Factor A; 0/vascular endothelial growth factor A, mouse; EC Endothelial Growth Factor Receptor-2

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