Key result
Cardiomyocyte-specific overexpression of Nrf2 prevented diabetic cardiomyopathy in mice by reducing myocardial fibrosis, inflammation, and oxidative stress.
Why the study?
The mechanisms underlying Nrf2 cardiac protection and its direct action on cardiomyocytes in diabetic cardiomyopathy were not well understood.
Does cardiomyocyte-specific overexpression of Nrf2 prevent diabetic cardiomyopathy in a type 1 diabetes mouse model?
Does cardiomyocyte-specific overexpression of Nrf2 prevent diabetic cardiomyopathy in a type 1 diabetes mouse model?
Cardiomyocyte-specific overexpression of Nrf2 protects against diabetic cardiomyopathy by improving glucose and lipid metabolism and reducing oxidative stress.
No change to clinical management of diabetic cardiomyopathy; leaves open Nrf2 activation as a target for translational studies.
Objective Metabolic disorders and oxidative stress are the main causes of diabetic cardiomyopathy. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts a powerful antioxidant effect and prevents the progression of diabetic cardiomyopathy. However, the mechanism of its cardiac protection and direct action on cardiomyocytes are not well understood. Methods In this study, cardiomyocyte-restricted Nrf2 transgenic mice (Nrf2-TG) were used to directly observe whether cardiomyocyte-specific overexpression of Nrf2 can prevent diabetic cardiomyopathy and correct glucose and lipid metabolism disorders in the heart. Results Compared to wild-type (WT) mice, Nrf2-TG mice showed resistance to diabetic cardiomyopathy in a streptozotocin (STZ)-induced type 1 diabetes mouse model. This was primarily manifested as improved echocardiography results as well as reduced myocardial fibrosis, cardiac inflammation, and oxidative stress. Conclusion These results showed that Nrf2 can directly act on cardiomyocytes to play a cardioprotective role. Mechanistically, the cardioprotective effects of Nrf2 depend on its antioxidation activity, partially through improving glucose and lipid metabolism by targeting the metabolic pathways of Akt/GSK-3 β/HK-II and AMPK/Sirt1/PGC-1α.
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Yang et al. (2022) studied Diabetic cardiomyopathy. Cardiomyocyte-specific overexpression of Nrf2 vs. Wild-type (WT) mice was evaluated on Echocardiography results, myocardial fibrosis, cardiac inflammation, and oxidative stress. Cardiomyocyte-specific overexpression of Nrf2 prevented diabetic cardiomyopathy in mice by reducing myocardial fibrosis, inflammation, and oxidative stress.
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