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Angiopoietin 1 expression levels in the myocardium direct coronary vessel development
Author(s) -
Ward Nicole L.,
Van Slyke Paul,
Sturk Celina,
Cruz Maribelle,
Dumont Daniel J.
Publication year - 2004
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.10479
Subject(s) - biology , angiopoietin 2 , angiopoietin , expression (computer science) , microbiology and biotechnology , medicine , endocrinology , cancer research , vascular endothelial growth factor , vegf receptors , computer science , programming language
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.