Emergence of Hydrogen Sulfide as an Endogenous Gaseous Signaling Molecule in Cardiovascular Disease

Long recognized as a malodorous and highly toxic gas, recent experimental studies have revealed that hydrogen sulfide (H 2 S) is produced enzymatically in all mammalian species including man and exerts several critical actions to promote cardiovascular homeostasis and health. During the past 15 years, scientists have determined that H 2 S is produced by 3 endogenous enzymes and exerts powerful effects on endothelial cells, smooth muscle cells, inflammatory cells, mitochondria, endoplasmic reticulum, and nuclear transcription factors. These effects have been reported in multiple organ systems, and the majority of data clearly indicate that H 2 S produced by the endogenous enzymes exerts cytoprotective actions. Recent preclinical studies investigating cardiovascular diseases have demonstrated that the administration of physiological or pharmacological levels of H 2 S attenuates myocardial injury, protects blood vessels, limits inflammation, and regulates blood pressure. H 2 S has emerged as a critical cardiovascular signaling molecule similar to nitric oxide and carbon monoxide with a profound effect on the heart and circulation. Our improved understanding of how H 2 S elicits protective actions, coupled with the rapid development of novel H 2 S-releasing agents, has resulted in heightened enthusiasm for the clinical translation of this ephemeral gaseous molecule. This review will examine our current state of knowledge about the actions of H 2 S within the cardiovascular system with an emphasis on the therapeutic potential and molecular cross talk between H 2 S, nitric oxide, and carbon monoxide.