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Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition

Normal blood flow is essential for proper heart formation during embryonic development, as abnormal hemodynamic load (blood pressure and shear stress) results in cardiac defects seen in congenital heart disease. However, the progressive detrimental remodeling processes that relate altered blood flow...

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Autores principales: Midgett, Madeline, López, Claudia S., David, Larry, Maloyan, Alina, Rugonyi, Sandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296359/
https://www.ncbi.nlm.nih.gov/pubmed/28228731
http://dx.doi.org/10.3389/fphys.2017.00056
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author Midgett, Madeline
López, Claudia S.
David, Larry
Maloyan, Alina
Rugonyi, Sandra
author_facet Midgett, Madeline
López, Claudia S.
David, Larry
Maloyan, Alina
Rugonyi, Sandra
author_sort Midgett, Madeline
collection PubMed
description Normal blood flow is essential for proper heart formation during embryonic development, as abnormal hemodynamic load (blood pressure and shear stress) results in cardiac defects seen in congenital heart disease. However, the progressive detrimental remodeling processes that relate altered blood flow to cardiac defects remain unclear. Endothelial–mesenchymal cell transition is one of the many complex developmental events involved in transforming the early embryonic outflow tract into the aorta, pulmonary trunk, interventricular septum, and semilunar valves. This study elucidated the effects of increased hemodynamic load on endothelial–mesenchymal transition remodeling of the outflow tract cushions in vivo. Outflow tract banding was used to increase hemodynamic load in the chicken embryo heart between Hamburger and Hamilton stages 18 and 24. Increased hemodynamic load induced increased cell density in outflow tract cushions, fewer cells along the endocardial lining, endocardium junction disruption, and altered periostin expression as measured by confocal microscopy analysis. In addition, 3D focused ion beam scanning electron microscopy analysis determined that a portion of endocardial cells adopted a migratory shape after outflow tract banding that is more irregular, elongated, and with extensive cellular projections compared to normal cells. Proteomic mass-spectrometry analysis quantified altered protein composition after banding that is consistent with a more active stage of endothelial–mesenchymal transition. Outflow tract banding enhances the endothelial–mesenchymal transition phenotype during formation of the outflow tract cushions, suggesting that endothelial–mesenchymal transition is a critical developmental process that when disturbed by altered blood flow gives rise to cardiac malformation and defects.
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spelling pubmed-52963592017-02-22 Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition Midgett, Madeline López, Claudia S. David, Larry Maloyan, Alina Rugonyi, Sandra Front Physiol Physiology Normal blood flow is essential for proper heart formation during embryonic development, as abnormal hemodynamic load (blood pressure and shear stress) results in cardiac defects seen in congenital heart disease. However, the progressive detrimental remodeling processes that relate altered blood flow to cardiac defects remain unclear. Endothelial–mesenchymal cell transition is one of the many complex developmental events involved in transforming the early embryonic outflow tract into the aorta, pulmonary trunk, interventricular septum, and semilunar valves. This study elucidated the effects of increased hemodynamic load on endothelial–mesenchymal transition remodeling of the outflow tract cushions in vivo. Outflow tract banding was used to increase hemodynamic load in the chicken embryo heart between Hamburger and Hamilton stages 18 and 24. Increased hemodynamic load induced increased cell density in outflow tract cushions, fewer cells along the endocardial lining, endocardium junction disruption, and altered periostin expression as measured by confocal microscopy analysis. In addition, 3D focused ion beam scanning electron microscopy analysis determined that a portion of endocardial cells adopted a migratory shape after outflow tract banding that is more irregular, elongated, and with extensive cellular projections compared to normal cells. Proteomic mass-spectrometry analysis quantified altered protein composition after banding that is consistent with a more active stage of endothelial–mesenchymal transition. Outflow tract banding enhances the endothelial–mesenchymal transition phenotype during formation of the outflow tract cushions, suggesting that endothelial–mesenchymal transition is a critical developmental process that when disturbed by altered blood flow gives rise to cardiac malformation and defects. Frontiers Media S.A. 2017-02-08 /pmc/articles/PMC5296359/ /pubmed/28228731 http://dx.doi.org/10.3389/fphys.2017.00056 Text en Copyright © 2017 Midgett, López, David, Maloyan and Rugonyi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Midgett, Madeline
López, Claudia S.
David, Larry
Maloyan, Alina
Rugonyi, Sandra
Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition
title Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition
title_full Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition
title_fullStr Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition
title_full_unstemmed Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition
title_short Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition
title_sort increased hemodynamic load in early embryonic stages alters endocardial to mesenchymal transition
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296359/
https://www.ncbi.nlm.nih.gov/pubmed/28228731
http://dx.doi.org/10.3389/fphys.2017.00056
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