CVD_CysSSSCys · Investigating the Therapeutic Potential of Persulfides: Implications of their Roles in Cardiovascular Disease

Cardiovascular disease (CVD) is the number one most fatal disease worldwide and despite many efforts, there is still no current treatment. Thus, the discovery of novel therapeutics to treat CVD is critical. Persulfides are biologically-relevant sulfur species that display much therapeutic potential in a variety of human disease, including CVD. Importantly, persulfides are potent scavengers of many disease-associated oxidants and electrophiles, making persulfides potentially relevant in the etiology of such diseases. Unfortunately, the reactive nature of persulfides makes their study difficult and reliant on the use of donor compounds. As a result, various persulfide donors have been developed, though these too often lack stability and are mostly biologically-irrelevant. Therefore, to address these issues, I discovered a novel persulfide donor, cysteine trisulfide (Cys-SSS-Cys). Cys-SSS-Cys is a stable biologically relevant molecule that upon reduction, releases cysteine persulfide (Cys-SSH), which is also a biologically relevant species. Thus, I hypothesize Cys-SSS-Cys is an ideal persulfide donor to study the therapeutic properties of persulfides, and that Cys-SSS-Cys will prove to be a novel therapeutic for the prevention and/or treatment of CVD. To assess this, I will examine effects of Cys-SSS-Cys on cellular, tissue and whole animal models displaying symptoms of CVD. First, I will identify mechanisms for cellular uptake and intracellular reduction of Cys-SSS-Cys to afford Cys-SSH. Next, I will measure the ability for Cys-SSS-Cys to prevent/treat markers associated with CVD in cells and tissue. Lastly, I will evaluate whether Cys-SSS-Cys serves as a therapeutic for CVD in whole animal models. Altogether, this research aims to identify Cys-SSS-Cys as a novel therapeutic to treat CVD; aiding in the advancement of global healthcare and the search for a cure to a devastating worldwide epidemic.