Cardiovascular Patterning as Determined by Hemodynamic Forces and Blood Vessel Genetics |
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Authors: | Gregory A. Anderson Ryan S. Udan Mary E. Dickinson R. Mark Henkelman |
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Affiliation: | 1. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.; 2. The Hospital For Sick Children, Toronto, Ontario, Canada.; 3. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.; Medical College of Wisconsin, UNITED STATES, |
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Abstract: | BackgroundVascular patterning depends on coordinated timing of arteriovenous specification of endothelial cells and the concomitant hemodynamic forces supplied by the onset of cardiac function. Using a combination of 3D imaging by OPT and embryo registration techniques, we sought to identify structural differences between three different mouse models of cardiovascular perturbation.ResultsEndoglin mutant mice shared a high degree of similarity to Mlc2a mutant mice, which have been shown to have a primary developmental heart defect causing secondary vessel remodeling failures. Dll4 mutant mice, which have well-characterized arterial blood vessel specification defects, showed distinct differences in vascular patterning when compared to the disruptions seen in Mlc2a-/- and Eng-/- models. While Mlc2a-/- and Eng-/- embryos exhibited significantly larger atria than wild-type, Dll4-/- embryos had significantly smaller hearts than wild-type, but this quantitative volume decrease was not limited to the developing atrium. Dll4-/- embryos also had atretic dorsal aortae and smaller trunks, suggesting that the cardiac abnormalities were secondary to primary arterial blood vessel specification defects.ConclusionsThe similarities in Eng-/- and Mlc2a-/- embryos suggest that Eng-/- mice may suffer from a primary heart developmental defect and secondary defects in vessel patterning, while defects in Dll4-/- embryos are consistent with primary defects in vessel patterning. |
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