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Role of DJ-1 in Modulating Glycative Stress in Heart Failure
- Source :
- Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
- Publication Year :
- 2020
-
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.
- Subjects :
- Glycation End Products, Advanced
Male
glycative stress
Protein Deglycase DJ-1
Myocardial Infarction
Disease
030204 cardiovascular system & hematology
Bioinformatics
Molecular Cardiology
03 medical and health sciences
Mice
0302 clinical medicine
Ischemia
medicine
Animals
Humans
030304 developmental biology
Early onset
Original Research
Heart Failure
Mice, Knockout
0303 health sciences
business.industry
medicine.disease
ischemic heart disease
Mice, Inbred C57BL
Disease Models, Animal
Oxidative Stress
Heart failure
Cardiology and Cardiovascular Medicine
business
Subjects
Details
- ISSN :
- 20479980
- Volume :
- 9
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of the American Heart Association
- Accession number :
- edsair.doi.dedup.....c8bdc0f972f5c0e5d2d6aa2548693946