Hydrogen sulfide and epigenetics: Novel insights into the cardiovascular effects of this gasotransmitter

Abstract

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 (H2S) 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 H2S‐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 H2S‐regulating epigenetic mechanisms, providing a panorama of the current literature, and offers a novel scenario for the development of H2S‐releasing ‘epidrugs’ with a potential clinical use in the prevention and treatment of many CV and non‐CV disorders.

Circulating Levels of Hydrogen Sulfide (H2S) in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis

“…This epigenetic alteration leads to an imbalance in the transsulfuration pathway as it reduces the conversion of homocysteine into cysteine, with the subsequent development of hyperhomocysteinemia, a recognized risk factor for vascular diseases [94,95]. At the same time, the reduced expression of CBS leads to a deficient biosynthesis of H 2 S. Which of hyperhomocysteinemia, impaired biosynthesis of H 2 S, or both is directly involved in the onset and progression of vascular diseases is not well established, but many studies support the use of compounds targeting the "H 2 S-system" in the treatment of hypertension [24,96], mainly due to the antihypertensive effects of the gasotransmitter [97] and its emerging role in the regulation of epigenetic mechanisms [98]. In addition, the impaired biosynthesis of H 2 S in patients with hypertension confirms the potential use of the sulfur gasotransmitter as a biomarker of the disease.…”