TY - JOUR
T1 - AA092, an annonaceous acetogenin mimetic, attenuates angiogenesis in a mouse model of inflammation-induced corneal neovascularization
AU - Zhang, Jing
AU - Zhou, Hongyan
AU - Jiang, Sheng
AU - Jin, Jiayi
AU - Li, Weihua
AU - Wang, Wencong
AU - Su, Shao Bo
N1 - Funding Information:
This project was supported in part by grants from the National Natural Science Foundation of China ( 31471122 ).
Publisher Copyright:
© 2015 Elsevier B.V.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2015/10
Y1 - 2015/10
N2 - Previous studies demonstrated that annonaceous acetogenin (AA) was an antitumor drug with anti-angiogenic activity. However, the effect of AA on ocular neovascular disorders remains unclear. The aim of the present study is to explore the effect of AA092, an annonaceous acetogenin mimetic, on corneal neovascularization (CNV). In a mouse model of alkali-induced CNV, topical application of AA092 to the injured corneas attenuated CNV. In addition, in vivo treatment with AA092 down-regulated the expression of the pro-angiogenic factors VEGF, b-FGF, TGFβ1, EGF but up-regulated the expression of the anti-angiogenic factors Thrombospondin-1 (Tsp-1), Tsp-2 and ADAMTS-1 in the injured corneas. Furthermore, AA092 inhibited the expression of pro-angiogenic factors, migration, proliferation and tube formation by human microvascular endothelial cells (HEMC-1) in vitro. These data indicate that AA092 has therapeutic potential for angiogenesis-associated diseases such as CNV.
AB - Previous studies demonstrated that annonaceous acetogenin (AA) was an antitumor drug with anti-angiogenic activity. However, the effect of AA on ocular neovascular disorders remains unclear. The aim of the present study is to explore the effect of AA092, an annonaceous acetogenin mimetic, on corneal neovascularization (CNV). In a mouse model of alkali-induced CNV, topical application of AA092 to the injured corneas attenuated CNV. In addition, in vivo treatment with AA092 down-regulated the expression of the pro-angiogenic factors VEGF, b-FGF, TGFβ1, EGF but up-regulated the expression of the anti-angiogenic factors Thrombospondin-1 (Tsp-1), Tsp-2 and ADAMTS-1 in the injured corneas. Furthermore, AA092 inhibited the expression of pro-angiogenic factors, migration, proliferation and tube formation by human microvascular endothelial cells (HEMC-1) in vitro. These data indicate that AA092 has therapeutic potential for angiogenesis-associated diseases such as CNV.
KW - AA092
KW - Angiogenesis
KW - Annonaceous acetogenin mimetics
KW - Corneal
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U2 - 10.1016/j.intimp.2015.08.009
DO - 10.1016/j.intimp.2015.08.009
M3 - Article
C2 - 26303770
AN - SCOPUS:84979180116
SN - 1567-5769
VL - 28
SP - 997
EP - 1002
JO - International immunopharmacology
JF - International immunopharmacology
IS - 2
ER -