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The Role Of Autophagy In Angiogenesis In Aortic Endothelial Cells
Author(s) -
Du Jianhai,
Teng RuJeng,
Guan Tongju,
Xu Hao,
Prichard Kirkwood A,
Shi Yang
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb519
Subject(s) - autophagy , angiogenesis , atg5 , microbiology and biotechnology , wound healing , autophagosome , protein kinase b , endothelial stem cell , chemistry , cancer research , biology , immunology , signal transduction , biochemistry , apoptosis , in vitro
Angiogenesis plays critical roles in the pathogenesis of ischemic heart diseases and peripheral vascular diseases. The objective of this study is to examine the role of autophagy in angiogenesis. Using cultured bovine aortic endothelial cells (BAEC), autophagy was induced either by nutrient‐deprivation or by overexpression of ATG5. Both treatments significantly increased autophagosome formation and increased expression of light chain3 II (LC3II). Interestingly, both nutrient‐deprivation and ATG5 overexpression increased EC tube formation, migration as well as wound‐healing process. To determine whether autphagy is required process for angiogenesis, EC were treated with a specific auotphagy inhibitor 3‐methyladenine (3‐MA) or Beclin‐1 siRNA to suppress autophagy activation. Interestingly, 3‐MA or Beclin‐1 siRNA greatly decreased EC tube formation, migration and wound‐healing under nutrient‐deprived conditions, and blocked VEGF‐induced tube formation and migration. Autophagy inhibition did not affect the expression of VEGF, PDGF and integrin αV. Furthermore, autophagy inhibition decreased AKT activation and ROS production, two important contributors to angiogenesis. In conclusion, we report for the first time that autophagy appears to be essential for angiogenesis and that targeting autophagy provides an important new route in treating cardiovascular diseases.