In this review, we summarize the knowledge pertaining to the role of epigenetics in the regulation of angiogenesis. In particular, we show that lysine acetylation and cytosine methylation are important transcriptional regulators of angiogenic genes in endothelial cells. Lysine acetylation and cytosine methylation inhibitors idiosyncratically tune the transcriptome and affect expression of key modulators of angiogenesis such as VEGF and eNOS. Transcriptomic profiling also reveals a series of novel genes that are concomitantly affected by epigenetic modulators. The reversibility and overall tolerability of currently available epigenetic inhibitors open up the prospect of therapeutic intervention in pathologies where angiogenesis is exacerbated. This type of multitargeted strategy has the major advantage of overcoming the compensatory feedback mechanisms that characterize single anti-angiogenic factors.
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