Evolution of Hydrogen Sulfide Therapeutics to Treat Cardiovascular Disease.

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