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PEDF improves cardiac function in rats subjected to myocardial ischemia/reperfusion injury by inhibiting ROS generation via PEDF‑R

  • Authors:
    • Qixiang Zhao
    • Zhiwei Liu
    • Bing Huang
    • Yanliang Yuan
    • Xiucheng Liu
    • Hu Zhang
    • Fan Qiu
    • Yiqian Zhang
    • Yufeng Li
    • Haoran Miao
    • Hongyan Dong
    • Zhongming Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China, Research Facility Center for Morphology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3243-3252
    |
    Published online on: March 9, 2018
       https://doi.org/10.3892/ijmm.2018.3552
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Abstract

The prevention and management of myocardial ischemia/reperfusion (MI/R) injury is an essential part of coronary heart disease surgery and is becoming a major clinical problem in the treatment of ischemic heart disease. Previous studies by our group have demonstrated that pigment epithelium‑derived factor (PEDF) improves cardiac function in rats with acute myocardial infarction and reduces hypoxia‑induced cell injury. However, the protective function and mechanisms underlying the effect of PEDF in MI/R injury remain to be fully understood. In the present study, the positive effect of PEDF in MI/R injury was confirmed by construction of the adult Sprague‑Dawley rat MI/R model. PEDF reduced myocardial infarct size and downregulated cardiomyocyte apoptosis in the I/R myocardium in this model. In addition, PEDF improved cardiac function and increased cardiac functional reserve in rats subjected to MI/R Injury. To further study the protective effect of PEDF and the underlying mechanisms in MI/R injury, a H9c2 cardiomyocyte hypoxia/reoxygenation (H/R) model was constructed. PEDF was confirmed to decrease H/R‑induced apoptosis in H9c2 cells, and this anti‑apoptotic function was abolished by pigment epithelium‑derived factor‑receptor (PEDF R) small interfering (si)RNA. Furthermore, administration of PEDF decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in H/R H9c2 cells. Compared with the H/R group, PEDF decreased mitochondrial ROS, increased the mitochondrial DNA copy number, reduced xanthine oxidase and NADPH oxidase activity, as well as RAC family small GTPase 1 protein expression. However, these effects of PEDF were markedly attenuated by PEDF‑R siRNA. To the best of our knowledge, the present study is the first to identify the protective effect of PEDF in MI/R injury, and confirm that the antioxidative effect PEDF occurred via inhibition of ROS generation via PEDF‑R under MI/R conditions.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao Q, Liu Z, Huang B, Yuan Y, Liu X, Zhang H, Qiu F, Zhang Y, Li Y, Miao H, Miao H, et al: PEDF improves cardiac function in rats subjected to myocardial ischemia/reperfusion injury by inhibiting ROS generation via PEDF‑R. Int J Mol Med 41: 3243-3252, 2018.
APA
Zhao, Q., Liu, Z., Huang, B., Yuan, Y., Liu, X., Zhang, H. ... Zhang, Z. (2018). PEDF improves cardiac function in rats subjected to myocardial ischemia/reperfusion injury by inhibiting ROS generation via PEDF‑R. International Journal of Molecular Medicine, 41, 3243-3252. https://doi.org/10.3892/ijmm.2018.3552
MLA
Zhao, Q., Liu, Z., Huang, B., Yuan, Y., Liu, X., Zhang, H., Qiu, F., Zhang, Y., Li, Y., Miao, H., Dong, H., Zhang, Z."PEDF improves cardiac function in rats subjected to myocardial ischemia/reperfusion injury by inhibiting ROS generation via PEDF‑R". International Journal of Molecular Medicine 41.6 (2018): 3243-3252.
Chicago
Zhao, Q., Liu, Z., Huang, B., Yuan, Y., Liu, X., Zhang, H., Qiu, F., Zhang, Y., Li, Y., Miao, H., Dong, H., Zhang, Z."PEDF improves cardiac function in rats subjected to myocardial ischemia/reperfusion injury by inhibiting ROS generation via PEDF‑R". International Journal of Molecular Medicine 41, no. 6 (2018): 3243-3252. https://doi.org/10.3892/ijmm.2018.3552
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao Q, Liu Z, Huang B, Yuan Y, Liu X, Zhang H, Qiu F, Zhang Y, Li Y, Miao H, Miao H, et al: PEDF improves cardiac function in rats subjected to myocardial ischemia/reperfusion injury by inhibiting ROS generation via PEDF‑R. Int J Mol Med 41: 3243-3252, 2018.
APA
Zhao, Q., Liu, Z., Huang, B., Yuan, Y., Liu, X., Zhang, H. ... Zhang, Z. (2018). PEDF improves cardiac function in rats subjected to myocardial ischemia/reperfusion injury by inhibiting ROS generation via PEDF‑R. International Journal of Molecular Medicine, 41, 3243-3252. https://doi.org/10.3892/ijmm.2018.3552
MLA
Zhao, Q., Liu, Z., Huang, B., Yuan, Y., Liu, X., Zhang, H., Qiu, F., Zhang, Y., Li, Y., Miao, H., Dong, H., Zhang, Z."PEDF improves cardiac function in rats subjected to myocardial ischemia/reperfusion injury by inhibiting ROS generation via PEDF‑R". International Journal of Molecular Medicine 41.6 (2018): 3243-3252.
Chicago
Zhao, Q., Liu, Z., Huang, B., Yuan, Y., Liu, X., Zhang, H., Qiu, F., Zhang, Y., Li, Y., Miao, H., Dong, H., Zhang, Z."PEDF improves cardiac function in rats subjected to myocardial ischemia/reperfusion injury by inhibiting ROS generation via PEDF‑R". International Journal of Molecular Medicine 41, no. 6 (2018): 3243-3252. https://doi.org/10.3892/ijmm.2018.3552
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