The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases

Figures

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  Figure 1. The enzymatic production of H2S is catalyzed by CSE, CBS, and 3-MPST. CSE catalyzes the production of H2S from the condensation of Hcy or the reaction of l-Cys and Hcy. Furthermore, 3-MPST synthesizes the gas from 3-MP produced from l-Cys by CAT. Additionally, CBS catalyzes the synthesis of H2S from two l-Cys molecules or l-Cys and Hcy reaction with the existence of CSE. Abbreviations: H2S: Hydrogen sulfide; Hcy: Homocysteine; l-Cys: l-cysteine; CSE: Cystathionine gamma lyase; CBS: Cystathionine beta synthase; 3-MPST: 3-mercaptopyruvate sulfur transferase; Glut: Glutamine; α-KG: Alpha-ketoglutarate; 3-MP: 3-mercaptopyruvate.

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  Figure 2. The summary of key pathways regulated by H2S donors in the treatment of CVDs. From left to right: H2S suppresses the activation of PERK/eIF2α/ATF4 pathway and its subsequent effects on ER stress. Next, H2S induces the elevation of Keap-1 by preventing its ubiquitylation, thereby promoting activation of the Keap-1/Nrf-2 pathway and the corresponding antioxidative features. Furthermore, H2S suppresses activation of the TGF-β/Smad-2/3 pathway to initiate anti-inflammatory properties. Next, H2S inhibits activation of the NF-қB pathway by preventing the phosphorylation of p65 and IқB-α degradation, thereby promoting anti-inflammatory activities. Moreover, H2S attenuates the phosphorylation of p38, resulting in inhibition of the pathway and elevation of anti-apoptotic and anti-oxidative properties. Next, H2S donors inhibit the activation of β-adrenergic receptors and their downstream effects on the stimulation of cAMP and blood pressure elevation. Additionally, H2S activates TPRV4 and KATP channels to mediate angiogenesis and vasodilation, thus regulating blood pressure. By activating TPRV4, H2S also activates the AMPK/mTOR pathway, thereby reducing autophagy. Besides, H2S activates…