Exacerbated Pulmonary Arterial Hypertension and Right Ventricular Hypertrophy in Animals With Loss of Function of Extracellular Superoxide Dismutase Academic Article uri icon

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  • Studies have demonstrated that increased oxidative stress contributes to the pathogenesis and the development of pulmonary artery hypertension (PAH). Extracellular superoxide dismutase (SOD3) is essential for removing extracellular superoxide anions, and it is highly expressed in lung tissue. However, it is not clear whether endogenous SOD3 can influence the development of PAH. Here we examined the effect of SOD3 knockout on hypoxia-induced PAH in mice and a loss-of-function SOD3 gene mutation (SOD3 E124D ) on monocrotaline (40 mg/kg)-induced PAH in rats. SOD3 knockout significantly exacerbated 2 weeks of hypoxia-induced right ventricular (RV) pressure and RV hypertrophy, whereas RV pressure in SOD3 knockout mice under normoxic conditions is similar to wild-type controls. In untreated control rats at age of 8 weeks, there was no significant difference between wild-type and SOD3 E124D rats in RV pressure and the ratio of RV weight:left ventricular weight (0.25±0.02 in wild-type rats versus 0.25±0.01 in SOD3 E124D rats). However, monocrotaline caused significantly greater increases of RV pressure in SOD3 E124D rats (48.6±1.8 mm Hg in wild-type versus 57.5±3.1 mm Hg in SOD3 E124D rats), of the ratio of RV weight:left ventricular weight (0.41±0.01 versus 0.50±0.09; P <0.05), and of the percentage of fully muscularized small arterioles in SOD3 E124D rats (55.2±2.3% versus 69.9±2.6%; P <0.05). Together, these findings indicate that the endogenous SOD3 has no role in the development of PAH under control conditions but plays an important role in protecting the lung from the development of PAH under stress conditions.


  • Xu, Dachun
  • Guo, Haipeng
  • Xu, Xin
  • Lu, Zhongbing
  • Fassett, John
  • Hu, Xinli
  • Xu, Yawei
  • Tang, Qizhu
  • Hu, Dayi
  • Somani, Arif
  • Geurts, Aron M
  • Ostertag, Eric
  • Bache, Robert J
  • Weir, E Kenneth
  • Chen, Yingjie

publication date

  • August 2011