title: Sestrin2 protects the myocardium against radiation-induced damage.
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.
authors.affiliation: Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China.
authors.forename: Yue-Can
authors.initials: YC
authors.lastname: Zeng
authors.affiliation: Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chi
authors.affiliation: Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xing
authors.affiliation: Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China.
authors.forename: Qiong-Yu
authors.initials: QY
authors.lastname: Duan
authors.affiliation: Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China.
authors.forename: Yu-Nan
authors.initials: YN
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Niu
authors.affiliation: Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China.
authors.forename: Mei-Yue
authors.initials: MY
authors.lastname: Tang
authors.affiliation: Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China. 511695796@qq.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
mesh_terms: D000818:Animals; D002196:Capillaries / Q000378:metabolism / Q000528:radiation effects; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005355:Fibrosis; D055786:Gene Knockout Techniques; D006321:Heart / Q000503:physiopathology / Q000528:radiation effects; D006439:Hemodynamics / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010544:Peroxidases; D011832:Radiation Injuries / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016019:Survival Analysis; D013997:Time Factors; D016277:Ventricular Function, Left / Q000528:radiation effects; D000084622:Sestrins
chemical_list: D009687:Nuclear Proteins; D010544:Peroxidases; C529380:Sesn2 protein, mouse; D000084622:Sestrins
keywords: Irradiation; Left ventricular ejection fraction; Radiation-induced heart disease; Sestrin2