Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage

Angiogenesis plays a critical role in embryo development, tissue repair, tumor growth and wound healing. In the present study, we investigated the role of the serine/threonine kinase Akt in angiogenesis. Silencing of Akt1 in human umbilical vein endothelial cells significantly inhibited vascular end...

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Autores principales: Ha, Jung Min, Jin, Seo Yeon, Lee, Hye Sun, Vafaeinik, Farzaneh, Jung, Yoo Jin, Keum, Hye Jin, Song, Sang Heon, Lee, Dong Hyung, Kim, Chi Dae, Bae, Sun Sik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443864/
https://www.ncbi.nlm.nih.gov/pubmed/30984553
http://dx.doi.org/10.1002/2211-5463.12621
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author Ha, Jung Min
Jin, Seo Yeon
Lee, Hye Sun
Vafaeinik, Farzaneh
Jung, Yoo Jin
Keum, Hye Jin
Song, Sang Heon
Lee, Dong Hyung
Kim, Chi Dae
Bae, Sun Sik
author_facet Ha, Jung Min
Jin, Seo Yeon
Lee, Hye Sun
Vafaeinik, Farzaneh
Jung, Yoo Jin
Keum, Hye Jin
Song, Sang Heon
Lee, Dong Hyung
Kim, Chi Dae
Bae, Sun Sik
author_sort Ha, Jung Min
collection PubMed
description Angiogenesis plays a critical role in embryo development, tissue repair, tumor growth and wound healing. In the present study, we investigated the role of the serine/threonine kinase Akt in angiogenesis. Silencing of Akt1 in human umbilical vein endothelial cells significantly inhibited vascular endothelial growth factor (VEGF)‐induced capillary‐like tube formation. Mice lacking Akt1 exhibited impaired retinal angiogenesis with delayed endothelial cell (EC) proliferation. In addition, VEGF‐induced corneal angiogenesis and tumor development were significantly inhibited in mice lacking Akt1. Loss of Akt1 resulted in reduced angiogenic sprouting, as well as the proliferation of ECs and mural cells. Addition of culture supernatant of vascular smooth muscle cells (VSMCs) in which Akt1 was silenced suppressed tube formation, the stability of preformed tubes and the proliferation of ECs. In addition, attachment of VSMCs to ECs was significantly reduced in cells in which Akt1 was silenced. Mural cell coverage of retinal vasculature was reduced in mice lacking Akt1. Finally, mice lacking Akt1 showed severe retinal hemorrhage compared to the wild‐type. These results suggest that the regulation of EC function and mural cell coverage by Akt1 is important for blood vessel maturation during angiogenesis.
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spelling pubmed-64438642019-04-12 Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage Ha, Jung Min Jin, Seo Yeon Lee, Hye Sun Vafaeinik, Farzaneh Jung, Yoo Jin Keum, Hye Jin Song, Sang Heon Lee, Dong Hyung Kim, Chi Dae Bae, Sun Sik FEBS Open Bio Research Articles Angiogenesis plays a critical role in embryo development, tissue repair, tumor growth and wound healing. In the present study, we investigated the role of the serine/threonine kinase Akt in angiogenesis. Silencing of Akt1 in human umbilical vein endothelial cells significantly inhibited vascular endothelial growth factor (VEGF)‐induced capillary‐like tube formation. Mice lacking Akt1 exhibited impaired retinal angiogenesis with delayed endothelial cell (EC) proliferation. In addition, VEGF‐induced corneal angiogenesis and tumor development were significantly inhibited in mice lacking Akt1. Loss of Akt1 resulted in reduced angiogenic sprouting, as well as the proliferation of ECs and mural cells. Addition of culture supernatant of vascular smooth muscle cells (VSMCs) in which Akt1 was silenced suppressed tube formation, the stability of preformed tubes and the proliferation of ECs. In addition, attachment of VSMCs to ECs was significantly reduced in cells in which Akt1 was silenced. Mural cell coverage of retinal vasculature was reduced in mice lacking Akt1. Finally, mice lacking Akt1 showed severe retinal hemorrhage compared to the wild‐type. These results suggest that the regulation of EC function and mural cell coverage by Akt1 is important for blood vessel maturation during angiogenesis. John Wiley and Sons Inc. 2019-03-20 /pmc/articles/PMC6443864/ /pubmed/30984553 http://dx.doi.org/10.1002/2211-5463.12621 Text en © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Ha, Jung Min
Jin, Seo Yeon
Lee, Hye Sun
Vafaeinik, Farzaneh
Jung, Yoo Jin
Keum, Hye Jin
Song, Sang Heon
Lee, Dong Hyung
Kim, Chi Dae
Bae, Sun Sik
Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage
title Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage
title_full Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage
title_fullStr Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage
title_full_unstemmed Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage
title_short Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage
title_sort vascular leakage caused by loss of akt1 is associated with impaired mural cell coverage
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443864/
https://www.ncbi.nlm.nih.gov/pubmed/30984553
http://dx.doi.org/10.1002/2211-5463.12621
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