Vincenzo Calderone

Epigenetics studies the heritable modifications of genome expression that do not affect the nucleotide sequence. Epigenetic modifications can be divided into: DNA methylation, histone modifications, and modulation of genome expression by non‐coding RNAs. Alteration of these mechanisms can alter the phenotype, and can lead to disease onset. The endogenous gasotransmitter hydrogen sulfide (H 2 S) plays pleiotropic roles in many systems, including the cardiovascular (CV) system, and its mechanism of action mainly includes S‐persulfidation of cysteine residues. Recent evidence suggests that many H 2 S‐mediated biological activities are based on the epigenetic regulation of cellular function, with effects ranging from DNA methylation to modification of histones and regulation of non‐coding RNAs. This review describes the role of H 2 S‐regulating epigenetic mechanisms, providing a panorama of the current literature, and offers a novel scenario for the development of H 2 S‐releasing ‘epidrugs’ with a potential clinical use in the prevention and treatment of many CV and non‐CV disorders.