Hydrogen sulfide as a vasculoprotective factor

Abstract

Hydrogen sulfide is a novel mediator with the unique properties of a gasotransmitter and many and varied physiological effects. Included in these effects are a number of cardiovascular effects that are proving beneficial to vascular health. Specifically, H2S can elicit vasorelaxation, prevention of inflammation and leukocyte adhesion, anti-proliferative effects and anti-thrombotic effects. Additionally, H2S is a chemical reductant and nucleophile that is capable of inhibiting the production of reactive oxygen species, scavenging and neutralising reactive oxygen species and boosting the efficacy of endogenous anti-oxidant molecules. These result in resistance to oxidative stress, protection of vascular endothelial function and maintenance of blood flow and organ perfusion. H2S has been shown to be protective in hypertension, atherosclerosis and under conditions of vascular oxidative stress, and deficiency of endogenous H2S production is linked to cardiovascular disease states. Taken together, these effects suggest that H2S has a physiological role as a vasculoprotective factor and that exogenous H2S donors may be useful therapeutic agents. This review article will discuss the vascular effects and anti-oxidant properties of H2S as well as examine the protective role of H2S in some important vascular disease states.

Figure 1

The balance between vascular relaxant and constrictor factors. The balance of vasoactive factors maintains vascular tone. Vasodilator factors also have anti-proliferative and anti-thrombotic effects, whereas vasoconstrictor factors tend to also have proliferative and/or pro-thrombotic effects. Increases in vasoconstrictor factors or decreases in vasorelaxant factors favour vascular contraction and other pathophysiological changes detrimental to vascular health [18]. PGI₂: prostacyclin, ET-1: endothelin-1, TXA₂: thromboxane A₂, AII: angiotensin II.

Figure 2

Sources of vascular reactive oxygen species and potential protective effects of H₂S. Schema showing the major vascular sources of superoxide, the parent reactive oxygen species. H₂S has been shown to inhibit A. NADPH oxidase activity and expression [39,40], B. mitochondrial ROS production [43], and possibly C. xanthine oxidase activity [74]. Additionally, H₂S has been reported to scavenge ROS [35-38] and also promote the actions of D. SOD [43] and E. GSH [41]. SOD: superoxide dismutase, MPO: myeloperoxidase, CAT: catalase, GPx: glutathione peroxidase, GSH: reduced glutathione, GSSG, oxidised glutathione.

Figure 3

Potential sites of vasculoprotective effects of H₂S. Cartoon depicting a cross section of the vascular wall showing the endothelium, intima containing smooth muscle cells overlaying the vascular media. A. H₂S has been shown to decrease leukocyte adhesion and migration [60] and differentiation to foam cells [64]. B. H₂S can inhibit the production of ROS [39,40] as well as scavenge ROS [35-38], protecting endothelial function. C H₂S prevents proliferation [66] and promotes apoptosis of vascular smooth muscle cells [67]D. H₂S prevents collagen deposition [51] and neo-intima formation [65]. E H₂S can inhibit platelet adhesion [26] and aggregation [25].