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.