Exacerbated pulmonary arterial hypertension and right ventricular hypertrophy in animals with loss of function of extracellular superoxide dismutase

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

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

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 (SOD3E124D) 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 SOD3E124D 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 rats). However, monocrotaline caused significantly greater increases of RV pressure in SOD3E124D rats (48.6±1.8 mm Hg in wild-type versus 57.5±3.1 mm Hg in SOD3E124D 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 SOD3E124D 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.

Original languageEnglish (US)
Pages (from-to)303-309
Number of pages7
JournalHypertension
Volume58
Issue number2
DOIs
StatePublished - Aug 1 2011

Keywords

  • Pulmonary artery hypertension
  • extracellular SOD
  • oxidative stress
  • right ventricular hypertrophy

Fingerprint Dive into the research topics of 'Exacerbated pulmonary arterial hypertension and right ventricular hypertrophy in animals with loss of function of extracellular superoxide dismutase'. Together they form a unique fingerprint.

  • Cite this