The Antiangiogenesis Role of Histone Deacetylase Inhibitors: Their Potential Application to Tumor Therapy and Tissue Repair.

Abstract

Angiogenesis, a process of new blood vessel formation from existing blood vessels, plays an important role in tumor growth and the tissue repair process. It is generally acknowledged that angiogenesis might contribute two both processes. In tumor growth, angiogenesis often increases oncogenic signaling, and in tissue repair, it decreases the stiffness of wound tissue and potentially exacerbates scar formation, resulting in pain and poor function. These poor outcomes are due to an increase in the expression of important genes involved in angiogenesis, such as hypoxia-inducible factor-1 alpha (HIF-1α) and its transcriptional target vascular endothelial growth factor (VEGF). Therefore, this adverse effect of angiogenesis should be taken into consideration. Limiting vessel growth instead of boosting growth may be beneficial for favorable long-term healing outcomes. Posttranslational modifications, including acetylation, which is mediated by histone acetyltransferases, and deacetylation, which is mediated by histone deacetylases (HDACs), are critical to HIF-1α function. Most studies have indicated that HDAC inhibitors (HDACIs) show great promise as antiangiogenic agents in the early phase of clinical trials. In this review, we discuss the role of the HDACs HIF-1α and VEGF in angiogenesis. Furthermore, we also discuss the molecular and cellular underpinnings of the effects of HDACIs on antiangiogenesis, which creates new avenues for anticancer therapeutics and the repair of wounded tissue.