Stabilization of Hypoxia Inducible Factor by DMOG Inhibits Development of Chronic Hypoxia-Induced Right Ventricular Remodeling.

  • Zhang S
  • Ma K
  • Liu Y
 et al. 
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Abstract

BACKGROUND One important determinant of longevity in congenital heart disease is right ventricular (RV) function, and this is especially true in cyanotic congenital heart disease. However, there is paucity of data concerning RV remodeling (RVR) in the setting of chronic hypoxia. Dimethyloxalglycine (DMOG) is a competitive inhibitor of hypoxia-inducible factor (HIF)-hydroxylated prolyl hydroxylase and has been shown to play an important role against ischemia-reperfusion myocardial injury. METHODS We tested the hypothesis that DMOG prevents the development RVR following chronic hypoxia exposure. Rats were injected with saline or DMOG and exposed to room air or continued hypoxia for 4 wk. In addition, we explored the response of myocardial erythropoietin and its receptor to hypoxic exposure. RESULTS Treatment with DMOG attenuated myocardial fibrosis, apoptosis, and oxidative stress, leading to enhanced RV contractile function. As an end point of HIF-dependent cardioprotection, a novel pathway in which nuclear factor kappa B links HIF-1 transcription was defined. CONCLUSIONS This study support a role for HIF-1 stabilizers in the treatment of RVR and bring into question the commonly held concept that RVR follows a linear relationship with increased RV afterload.

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Authors

  • Sen Zhang

  • Kai Ma

  • Yiwei Liu

  • Xiangbin Pan

  • Qiuming Chen

  • Lei Qi

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