Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage
Jung Min Ha,
Seo Yeon Jin,
Hye Sun Lee,
Farzaneh Vafaeinik,
Yoo Jin Jung,
Hye Jin Keum,
Sang Heon Song,
Dong Hyung Lee,
Chi Dae Kim,
Sun Sik Bae
Affiliations
Jung Min Ha
Biomedical Research Institute Gene and Cell Therapy Center for Vessel Associated Disease Department of Pharmacology Pusan National University School of Medicine Yangsan Korea
Seo Yeon Jin
Biomedical Research Institute Gene and Cell Therapy Center for Vessel Associated Disease Department of Pharmacology Pusan National University School of Medicine Yangsan Korea
Hye Sun Lee
Biomedical Research Institute Gene and Cell Therapy Center for Vessel Associated Disease Department of Pharmacology Pusan National University School of Medicine Yangsan Korea
Farzaneh Vafaeinik
Biomedical Research Institute Gene and Cell Therapy Center for Vessel Associated Disease Department of Pharmacology Pusan National University School of Medicine Yangsan Korea
Yoo Jin Jung
Biomedical Research Institute Gene and Cell Therapy Center for Vessel Associated Disease Department of Pharmacology Pusan National University School of Medicine Yangsan Korea
Hye Jin Keum
Biomedical Research Institute Gene and Cell Therapy Center for Vessel Associated Disease Department of Pharmacology Pusan National University School of Medicine Yangsan Korea
Sang Heon Song
Biomedical Research Institute Department of Internal Medicine Pusan National University Hospital Busan Korea
Dong Hyung Lee
Department of Gynecology and Obstetrics Pusan National University Yangsan Hospital Korea
Chi Dae Kim
Biomedical Research Institute Gene and Cell Therapy Center for Vessel Associated Disease Department of Pharmacology Pusan National University School of Medicine Yangsan Korea
Sun Sik Bae
Biomedical Research Institute Gene and Cell Therapy Center for Vessel Associated Disease Department of Pharmacology Pusan National University School of Medicine Yangsan Korea
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.
