Cardiovascular diseases (CVD) continue to be the leading cause of death in the world despite recent therapeutic advances. Although many CVDs remain incurable, enormous efforts have been placed in harnessing angiogenesis as therapeutics for these diseases. Epigenetics, the modification of gene expression post-transcriptionally and post-translationally, are important in regulating many biological processes. One of the main post-translational epigenetic modifications, modification of chromatin structure by the acetylation of histone tails within the chromatin by either histone deacetylases (HDACs) or histone acetyltransferases (HATs), is important in modulating gene transcription and has emerged as an important regulatory player from pathogenesis to therapeutics in CVDs. Particularly, HDACs, which are largely involved in promoting chromatin compaction and hence inhibitions of gene transcription, have been implicated in the pathogenic signalling underlying many aspects of CVDs. Recently, histone modifications have been demonstrated to play important roles in the angiogenesis process. Pharmacological inhibitions of HDACs have displayed promising therapeutic potentials in several pre-clinical models of CVDs where angiogenesis is of paramount importance. There are many evidences proving that pro- and anti-angiogenic therapies—and the impact of epigenetics in these processes—can help to artificially reconstruct the vasculature in patients with cardiovascular diseases. Conversely, utilising knowledge of HDACs in angiogenesis might help to develop anti-angiogenic therapies in tackling diseases that are characterised with excessive pathological angiogenesis, including cancer and age-related macular degeneration. Understanding the molecular mechanisms underlying HDACs in modulating angiogenesis will undoubtedly benefit future therapeutics development. This chapter focuses on the emerging role of HDACs in angiogenesis and discuss their potentials and challenges in utilising HDAC inhibitors as therapeutics in several major cardiovascular diseases.
Part of the book: Physiologic and Pathologic Angiogenesis