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Sestrin2 protects the myocardium against radiation-induced damage
Yue-Can Zeng1, Feng Chi1, Rui Xing1
1Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China.
Abstract:
The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury.
Insights
Sestrin2 deficiency exacerbates radiation-induced heart injury and cardiomyopathy in mice. Overexpressing Sestrin2 may protect against radiation damage, highlighting its therapeutic potential for heart conditions.
Area of Science:
- Cardiology
- Radiation Oncology
- Molecular Biology
Background:
- Radiation therapy can cause significant cardiac side effects, including cardiomyopathy.
- Sestrin2 is a protein involved in cellular stress responses.
Purpose of the Study:
- To investigate the role of Sestrin2 in radiation-induced heart injury.
- To determine Sestrin2's impact on the development of cardiomyopathy after irradiation.
Main Methods:
- Utilized Sestrin2 knockout mice and irradiation models (15 or 22 Gy).
- Assessed cardiac function using echocardiography and left ventricular catheterization.
- Quantified myocardial fibrosis and capillary density via Masson's trichrome and immunohistochemistry/Western blot.
Main Results:
- Irradiation impaired left ventricular ejection fraction (LVEF) in wild-type mice.
- Sestrin2 knockout mice showed exacerbated LVEF reduction post-irradiation.
- Both wild-type and Sestrin2 knockout mice exhibited increased myocardial fibrosis and decreased capillary density after irradiation.
Conclusions:
- Sestrin2 plays a role in regulating radiation-induced cardiomyopathy, particularly myocardial fibrosis.
- Sestrin2 deficiency worsens cardiac injury following irradiation.
- Overexpression of Sestrin2 may offer a protective strategy against radiation-induced myocardial damage.
