Histone deacetylases (HDACs) regulate gene transcription by modifying the acetylation level of histone and nonhistone proteins. In this study, we examined the effect of largazole, an inhibitor of class I HDACs, on inflammatory corneal angiogenesis. In a mouse model of alkali-induced corneal neovascularization (CNV), topical application of largazole to the injured corneas attenuated CNV. In addition, in vivo treatment with largazole down-regulated the expression of the pro-angiogenic factors VEGF, b-FGF, TGFβ1 and 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, largazole 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 largazole has therapeutic potential for angiogenesis-associated diseases.
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