Work

Role of DJ‐1 in Modulating Glycative Stress in Heart Failure

Year: 2020

Type: article

Abstract: Background DJ-1 is a ubiquitously expressed protein typically associated with the development of early onset Parkinson disease. Recent data suggest that it also plays a role in the cellular response to stress. Here, we sought to determine the role DJ-1 plays in the development of heart failure. Methods and Results Initial studies found that DJ-1 deficient mice (DJ-1 knockout; male; 8-10 weeks of age) exhibited more severe left ventricular cavity dilatation, cardiac dysfunction, hypertrophy, and fibrosis in the setting of ischemia-reperfusion-induced heart failure when compared with wild-type littermates. In contrast, the overexpression of the active form of DJ-1 using a viral vector approach resulted in significant improvements in the severity of heart failure when compared with mice treated with a control virus. Subsequent studies aimed at evaluating the underlying protective mechanisms found that cardiac DJ-1 reduces the accumulation of advanced glycation end products and activation of the receptor for advanced glycation end products-thus, reducing glycative stress. Conclusions These results indicate that DJ-1 is an endogenous cytoprotective protein that protects against the development of ischemia-reperfusion-induced heart failure by reducing glycative stress. Our findings also demonstrate the feasibility of using a gene therapy approach to deliver the active form of DJ-1 to the heart as a therapeutic strategy to protect against the consequences of ischemic injury, which is a major cause of death in western populations.

Source: Journal of the American Heart Association

DOI: 10.1161/jaha.119.014691