Open Access

Upregulated ATF6 contributes to chronic intermittent hypoxia-afforded protection against myocardial ischemia/reperfusion injury

  • Authors:
    • Weikun Jia
    • Zhao Jian
    • Jingwei Li
    • Lin Luo
    • Liang Zhao
    • Yang Zhou
    • Fuqin Tang
    • Yingbin Xiao
  • View Affiliations

  • Published online on: March 22, 2016     https://doi.org/10.3892/ijmm.2016.2535
  • Pages: 1199-1208
  • Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In the present study, we investigated the role of activating transcription factor 6 (ATF6) in the mechanism by which chronic intermittent hypoxia (CIH) increases tolerance to myocardial ischemia/reperfusion (I/R). Experiments were conducted using a rat model of I/R injury in vivo and isolated Langendorff-perfused rat hearts ex vivo. The role of Akt in this process was also investigated in vitro using rat myoblast H9c2 cells. Cell viability was measured using a cell counting kit-8 assay. Lactate dehydrogenase (LDH) and creatine kinase cardiac isoenzyme activity were also measured as markers of cellular damage. ATF6, Akt and phosphorylated (p)-Akt expression was analyzed by western blot analysis. RNA interference (RNAi) was used to suppress ATF6 expression. We noted that ATF6 expression in the ventricular myocardium was significantly increased in rats exposed to CIH. Furthermore, we noted that CIH preserved cardiac function after I/R in vivo and improved post-ischemic recovery of myocardial performance in isolated rat hearts. ATF6 and p-Akt expression was upregulated in cultured H9c2 cells exposed to chronic mild hypoxia compared with those cultured under normoxic conditions. Chronic mild hypoxia attenuated subsequent simulated I/R injury in H9c2 cells (48 h), as evidenced by increased cell viability and decreased LDH activity. By contrast, decreased cell viability and increased LDH activity were observed in siRNA-ATF6-transfected H9c2 cells, with a concomitant reduction in p-Akt levels. These results indicated that ATF6 upregulation is involved in the mechanism by which CIH attenuates myocardial I/R injury, possibly through upregulation of p-Akt, which is a key regulator of cardiomyocyte survival.
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May-2016
Volume 37 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Jia W, Jian Z, Li J, Luo L, Zhao L, Zhou Y, Tang F and Xiao Y: Upregulated ATF6 contributes to chronic intermittent hypoxia-afforded protection against myocardial ischemia/reperfusion injury. Int J Mol Med 37: 1199-1208, 2016
APA
Jia, W., Jian, Z., Li, J., Luo, L., Zhao, L., Zhou, Y. ... Xiao, Y. (2016). Upregulated ATF6 contributes to chronic intermittent hypoxia-afforded protection against myocardial ischemia/reperfusion injury. International Journal of Molecular Medicine, 37, 1199-1208. https://doi.org/10.3892/ijmm.2016.2535
MLA
Jia, W., Jian, Z., Li, J., Luo, L., Zhao, L., Zhou, Y., Tang, F., Xiao, Y."Upregulated ATF6 contributes to chronic intermittent hypoxia-afforded protection against myocardial ischemia/reperfusion injury". International Journal of Molecular Medicine 37.5 (2016): 1199-1208.
Chicago
Jia, W., Jian, Z., Li, J., Luo, L., Zhao, L., Zhou, Y., Tang, F., Xiao, Y."Upregulated ATF6 contributes to chronic intermittent hypoxia-afforded protection against myocardial ischemia/reperfusion injury". International Journal of Molecular Medicine 37, no. 5 (2016): 1199-1208. https://doi.org/10.3892/ijmm.2016.2535