Open AccessVascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage
Author(s) -
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
Publication year - 2019
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12621
Subject(s) - angiogenesis , mural cell , akt1 , endothelial stem cell , protein kinase b , umbilical vein , sprouting angiogenesis , microbiology and biotechnology , biology , cell growth , cancer research , vascular smooth muscle , endocrinology , chemistry , neovascularization , signal transduction , biochemistry , in vitro , smooth muscle
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 EC s and mural cells. Addition of culture supernatant of vascular smooth muscle cells ( VSMC s) in which Akt1 was silenced suppressed tube formation, the stability of preformed tubes and the proliferation of EC s. In addition, attachment of VSMC s to EC s 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.