Angiopoietin 1 expression levels in the myocardium direct coronary vessel development

Mutational studies in genetically engineered mice have shown that the angiopoietin/Tie2(Tek) signaling pathway is indispensable for vascular development. To further investigate the role of Angiopoietin 1 in heart development, we developed transgenic mice that express Angiopoietin 1 under control of...

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Bibliographic Details
Published in:Developmental dynamics 2004-03, Vol.229 (3), p.500-509
Main Authors: Ward, Nicole L., Van Slyke, Paul, Sturk, Celina, Cruz, Maribelle, Dumont, Daniel J.
Format: Article
Language:English
Subjects:
angiogenesis
Angiopoietin-1 - biosynthesis
Angiopoietin-1 - metabolism
Angiopoietin-1 - physiology
Animals
Blotting, Western
Cadherins - metabolism
conditional expression
coronary vessels
Coronary Vessels - embryology
Coronary Vessels - pathology
Developmental Biology - methods
doxycycline
Doxycycline - pharmacology
Gene Expression Regulation, Developmental
Genotype
heart
Heart - embryology
Hemorrhage
Immunohistochemistry
Mice
Mice, Transgenic
Models, Genetic
Myocardium - pathology
Pericardium - metabolism
Precipitin Tests
Signal Transduction
Tie2/Tek
Time Factors
transgenic
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Summary:Mutational studies in genetically engineered mice have shown that the angiopoietin/Tie2(Tek) signaling pathway is indispensable for vascular development. To further investigate the role of Angiopoietin 1 in heart development, we developed transgenic mice that express Angiopoietin 1 under control of doxycycline in cardiac myocytes. Ninety percent of all transgenic mice die between embryonic day 12.5 and 15.5. Beginning at embryonic day 12.5, transgenic mice exhibit dilated atria, a significant thinning of the myocardial wall, and eventual outflow tract collapse. In addition, hearts of the most severely affected transgenic embryos have no coronary arteries as a result of the defective development and maintenance of the epicardium. The subsequent lack of blood and nutrient delivery to the developing heart may account for decreases in N‐cadherin expression and subsequent loss of cell–cell contact leading to cell death, and ultimately the collapse and hemorrhage of the heart. These results suggest a pivotal role for Angiopoietin 1 in cardiovascular development, specifically the development of the epicardium and coronary vasculature. Developmental Dynamics 229:500–509, 2004. © 2004 Wiley‐Liss, Inc.
ISSN:1058-8388
1097-0177
DOI:10.1002/dvdy.10479