Evolution of Hydrogen Sulfide Therapeutics to Treat Cardiovascular Disease

Hydrogen sulfide (H₂S)-a potent gaseous signaling molecule-has emerged as a critical regulator of cardiovascular homeostasis. H₂S is produced enzymatically by 3 constitutively active endogenous enzymes in all mammalian species. Within the past 2 decades, studies administering H₂S-donating agents and the genetic manipulation of H₂S-producing enzymes have revealed multiple beneficial effects of H₂S, including vasodilation, activation of antiapoptotic and antioxidant pathways, and anti-inflammatory effects. More recently, the heightened enthusiasm in this field has shifted to the development of novel H₂S-donating agents that exert favorable pharmacological profiles. This has led to the discovery of novel H₂S-mediated signaling pathways. This review will discuss recently developed H₂S therapeutics, introduce signaling pathways that are influenced by H₂S-dependent sulfhydration, and explore the dual-protective effect of H₂S in cardiorenal syndrome.