Vascular biology of hydrogen sulfide

Abstract

Hydrogen sulfide (H₂S) is a ubiquitous signaling molecule with important functions in many mammalian organs and systems. Observations in the 1990s ascribed physiological actions to H₂S in the nervous system, proposing that this gasotransmitter acts as a neuromodulator. Soon after that, the vasodilating properties of H₂S were demonstrated. In the past decade, H₂S was shown to exert a multitude of physiological effects in the vessel wall. H₂S is produced by vascular cells and exhibits antioxidant, antiapoptotic, anti-inflammatory, and vasoactive properties. In this concise review, we have focused on the impact of H₂S on vascular structure and function with an emphasis on angiogenesis, vascular tone, vascular permeability and atherosclerosis. H₂S reduces arterial blood pressure, limits atheromatous plaque formation, and promotes vascularization of ischemic tissues. Although the beneficial properties of H₂S are well established, mechanistic insights into the molecular pathways implicated in disease prevention and treatment remain largely unexplored. Unraveling the targets and downstream effectors of H₂S in the vessel wall in the context of disease will aid in translation of preclinical observations. In addition, acute regulation of H₂S production is still poorly understood and additional work delineating the pathways regulating the enzymes that produce H₂S will allow pharmacological manipulation of this pathway. As the field continues to grow, we expect that H₂S-related compounds will find their way into clinical trials for diseases affecting the blood vessels.

Keywords: blood vessels; endothelium; hydrogen sulfide; signaling; vascular smooth muscle.

Fig. 1.

Timescale of H₂S effects. Acute effects of H₂S include activation/inhibition of ion channels, kinases, and other enzymes. These events are observed within a few seconds and up to several minutes after exposure to H₂S. Chronic effects are dependent on gene expression and involve altered transcription factor activity; although activation/inhibition of transcription factors might be observed within minutes to hours after H₂S administration, the biological effects are not observed until after much later, requiring up to days to manifest. It should be noted that phosphorylation is secondary to activation of a kinase or inhibition of a phosphatase, through persulfidation or other mechanisms.

Fig. 2.

Summary of biological activity of H₂S in vascular cells.