title: AA092, an annonaceous acetogenin mimetic, attenuates angiogenesis in a mouse model of inflammation-induced corneal neovascularization.
abstract: 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.
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors: Jing
authors: J
authors: Zhang
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors: Hongyan
authors: H
authors: Zhou
authors: Guangzhou Institute of Biomedicine and Health, CAS, Guangzhou 510663, China.
authors: Sheng
authors: S
authors: Jiang
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors: Jiayi
authors: J
authors: Jin
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors: Weihua
authors: W
authors: Li
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors: Wencong
authors: W
authors: Wang
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors: Shao Bo
authors: SB
authors: Su
mesh_terms: D054378:Acetogenins / Q000008:administration & dosage* / Q000009:adverse effects; D000468:Alkalies / Q000378:metabolism; D000818:Animals; D029061:Annonaceae; D032701:Biomimetics; D002460:Cell Line; D003315:Cornea / Q000187:drug effects* / Q000502:physiology; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D054378:Acetogenins; D000468:Alkalies; D036341:Intercellular Signaling Peptides and Proteins
keywords: AA092; Angiogenesis; Annonaceous acetogenin mimetics; Corneal