Upregulation of FoxM1 protects against ischemia/reperfusion-induced myocardial injury

Gang Zhang; Kun  Yu; Zhi  Bao; Xiaofeng  Sun; Dongying  Zhang

doi:10.18388/abp.2020_5536

Gang Zhang Department of Cardiology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai ‘an, Jiangsu Province, 223300, China;
Kun Yu Department of Cardiology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai ‘an, Jiangsu Province, 223300, China;
Zhi Bao Department of Cardiology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai ‘an, Jiangsu Province, 223300, China;
Xiaofeng Sun Department of Pediatric, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai ‘an, Jiangsu Province, 223300, China
Dongying Zhang Department of Cardiology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai ‘an, Jiangsu Province, 223300, China;

DOI: https://doi.org/10.18388/abp.2020_5536

Abstract

Background. Ischemia/reperfusion (I/R) induced lethal tissue injury in myocardium. FoxM1 (Forkhead Box M1), expressed in proliferating cardiac progenitor cells, could regulate myocardial development. However, the role of FoxM1 in I/R-induced myocardial injury has not been reported yet. Methods. Rats were conducted with regional ischemia followed by reperfusion in myocardium through ligation of the left anterior descending coronary artery. Triphenyl-tetrazolium chloride staining was utilized to assess the infarct size. ELISA was performed to detect activities of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Protein expression of FoxM1 in heart tissues and H9c2 were determined by western blot. H9c2 cells were used to establish a hypoxia/reoxygenation cell model, and the cell viability, proliferation and apoptosis were evaluated by MTT, EdU (5-ethynyl-2’-deoxyuridine) staining and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, respectively. Adenovirus (Ad)-mediated over-expression of FoxM1 was injected into the anterior wall of the left ventricle of rats to evaluate the role of FoxM1 on in vivo I/R-induced myocardial injury. Results. FoxM1 was reduced in heart tissues isolated from rats post myocardial I/R injury. Forced FoxM1 expression increased cell viability and proliferation of hypoxia/reoxygenation-induced H9c2, while repressed the cell apoptosis with increased Bcl-2 and decreased Bax and cleaved caspase-3. Injection of Ad-FoxM1 suppressed infarct size of the heart and decreased activities of CK-MB and LDH. Conclusion. FoxM1 attenuated I/R-induced myocardial injury, providing potential therapeutic target for the disease.