| Autor: |
Soo Yeon An, Seon‐Ah Jin, Hee Jeong Seo, Yu Ran Lee, Sungmin Kim, Byeong Hwa Jeon, Jin‐Ok Jeong |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
ESC Heart Failure, Vol 11, Iss 2, Pp 1182-1193 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2055-5822 |
| DOI: |
10.1002/ehf2.14686 |
| Popis: |
Abstract Aims The clinical application of doxorubicin (DOX), a potent anthracycline anticancer drug that effectively treats various malignancies, is limited by its side effects, such as cardiomyopathy. Apurinic/apyrimidinic endonuclease 1/redox factor‐1 (APE1/Ref‐1) is a multifunctional protein that can be secreted and is a promising target for the reduction of DOX‐induced inflammation and oxidative stress. We aimed to investigate the protective role of secretory APE1/Ref‐1 against DOX‐induced cardiac injury. Methods and results Designated adenoviral preprotrypsin‐leading sequence APE1/Ref‐1 (Ad‐PPTLS‐APE1/Ref‐1) was used to overexpress secretory APE1/Ref‐1 and assess its role in preventing DOX‐induced cardiomyopathy in vitro. Our findings revealed that exposure to secretory APE1/Ref‐1 significantly decreased N‐terminal pro‐B‐type natriuretic peptide levels in DOX‐treated H9C2 cells. In addition, secretory APE1/Ref‐1 reduced the severity of cardiomyocyte injury and apoptosis in both in vitro and in vivo DOX‐induced cardiotoxicity models. The observed cardioprotective effects of secretory APE1/Ref‐1 were mediated via inhibition of the p53 signalling pathway and enhancement of cell viability through attenuation of oxidative stress in DOX‐treated cardiomyocytes. Conclusions Our study provides evidence that secretory APE1/Ref‐1 has the potential to inhibit DOX‐induced cardiac toxicity by inhibiting oxidative stress and p53 related apoptosis both in vitro and in vivo. These findings suggest that secretory APE1/Ref‐1 supplementation is a promising strategy to attenuate DOX‐induced cardiomyocyte damage in a preclinical model. Further clinical investigations are essential to validate the therapeutic efficacy and safety of the intervention in human subjects. |
| Databáze: |
Directory of Open Access Journals |
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