Exploring the Cardioprotective Potential of Hydropersulfides

Hydrogen sulfide (H2S) has earned much attention over the past three decades because of its cytoprotective pharmacological effects. However, the molecular mechanisms of H2S activity are poorly understood. An original hypothesis was that H2S behaves similarly to the “gasotransmitters”, carbon monoxide (CO) and nitric oxide (NO), hinging on the direct antioxidant properties of H2S, but later studies have found that this is likely only part of the story. More recently, the literature suggests that hydropersulfides (RSSH) are the products of hydrogen sulfide (H2S)-mediated thiol (RSH) modification indicating possible signaling and/or protective capabilities. We now know that hydropersulfides along with polysulfides and other sulfane sulfur species are ubiquitous in mammalian systems and represent an emerging field of reactive sulfur species (RSS). Specifically, RSSH is largely found in highly metabolizing tissue such as the heart and vasculature. Herein, we present the investigation of various RSS, focusing on RSSH, and their cardioprotective properties using myocardial ischemia-reperfusion injury (Chapter 3) and anthracycline-induced cardiotoxicity (Chapter 4) as clinically relevant models