Histone Deacetylase Inhibitor Trichostatin A Reduces Endothelial Cell Proliferation by Suppressing STAT5A-Related Gene Transcription.

Inhibitors of histone deacetylases (HDACi) have shown promising effects in preclinical applications for the treatment of many diseases. Confusedly though, the effects of the HDACi trichostatin A (TSA) on angiogenesis are variable among different diseases. This study investigated the direct effects of TSA on endothelial cells, which plays essential roles in angiogenesis and the underlying molecular events. TSA reduced the viability of human umbilical vein endothelial cells (HUVECs), in which proliferation-related genes including , , and were found to be involved. Furthermore, signal transducer and activator of transcription 5 A (STAT5A) was demonstrated to be reduced by TSA and to mediate TSA-induced downregulation of , , and and HUVEC proliferation. Mechanistically, data showed that STAT5A directly bound to the promoters of , , and and activated their transcription through special DNA sequence sites. Finally, the TSA-STAT5A-, , and axis also worked in a cancerous endothelial cell angiogenesis model. The results of this study revealed novel mechanisms underlying the effects of TSA on endothelial cells and provided insights for angiogenesis-associated diseases.