Abstract: Impact of Oxidative Stress on Heart Health

Human cardiomyocytes (CMs) undergo a significant amount of oxidative stress, negatively impacting hearts' contractile force. Accumulation of oxidative stress or DNA damage within CMs can lead to cancer, cardiovascular disease, or stroke. The human FANCJ helicase is involved with multiple DNA repair pathways, specifically interstrand DNA crosslinks and oxidative stress. It was previously established that FANCJ could recognize and bind to an 8-oxoguanine modified DNA (8-oxoG4s) sequence caused by oxidative damage. Oxidative stress and DNA damage have been linked to cardiovascular disease, but the exact mechanisms of repaired in CMs are not well defined. The central hypothesis is that FANCJ can rescue cardiomyocytes' contractile function damaged by oxidative stress or different forms of DNA lesions. To test this, I first determined the sensitivity of CMs to oxidative stress and other DNA damage forms by using viability, contractility, and single-cell electrophoresis assays. Second, I determined if FANCJ can rescue the contractility of CMs after exposure to oxidative damage and DNA damage. Cells that overexpress FANCJ can readily overcome the chemical stress induced by hydrogen peroxide treatment. On the contrary, cells that produce a FANCJ mutant, which cannot interact with G4s, resulted in an accumulation of 8oxoG4s. Based on this evidence, FANCJ plays a vital role in alleviating the damage caused by oxidative stress. These experimental outcomes can be collectively used to develop new screen methods for patients who may be predisposed to FANCJ-associated cardiovascular diseases.