title: Suberoylanilide hydroxamic acid suppresses inflammation-induced neovascularization.
abstract: Histone deacetylases (HDACs) regulate gene transcription by modifying the acetylation of histone and nonhistone proteins. Deregulated expression of HDACs has been implicated in tumorigenesis and angiogenesis. In this study, we examined the effect of suberoylanilide hydroxamic acid (SAHA), a potent inhibitor of HDACs, on inflammatory corneal angiogenesis. In a mouse model of alkali-induced corneal neovascularization (CNV), topical application of SAHA to the injured corneas attenuated CNV. In addition, in vivo treatment with SAHA downregulated the expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGFβ1), and epidermal growth factor (EGF), but upregulated the expression of the anti-angiogenic factors thrombospondin (TSP)-1, TSP-2, and ADAMTS-1 in the injured corneas. Furthermore, SAHA 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 SAHA has therapeutic potential for CNV.
authors.affiliation: a The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Sun Yat-sen University, 54 S Xianlie Road, Guangzhou 510060, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhou
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
authors.forename: Shao Bo
authors.initials: SB
authors.lastname: Su
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071097:ADAMTS1 Protein; D060433:Administration, Ophthalmic; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003315:Cornea / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D006655:Histone Deacetylases / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007249:Inflammation / Q000150:complications / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D019699:Thrombospondins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000077337:Vorinostat; D000099262:Thrombospondin 2
chemical_list: D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004815:Epidermal Growth Factor; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D019699:Thrombospondins; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D000077337:Vorinostat; D000099262:Thrombospondin 2; C481348:SPZ1 protein, human; C103859:ADAMTS1 protein, human
keywords: CNV; HDAC; HDACs; NVC; SAHA; angiogenesis; angiogenèse