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GW24-e0233 NADPHoxidase4-mediated myocardial damage effects to heart failure in rats through the modulation of oxidative stress and cardiac remodelling
  1. Wang Yong,
  2. Chun Li,
  3. Yulin Ouyang,
  4. Tianjiao Shi,
  5. Wenjing Chuo,
  6. Xiaomin Yang,
  7. Binghua Tang,
  8. Wei Wang,
  9. Wang Wei
  1. University of Chinese Medicine, Beijing


Objectives We aim to investigate the myocardial injury effects of different NADPH oxidase subtypes on a rat heart failure (HF) model and possible underlying mechanism.

Methods HF model were induced by ligation of left anterior descending coronary (LAD) in Sprague-Dawley rats. 2 groups were divided: CHD group (LAD ligation) and control group. After 4 weeks, rats were sacrificed for cardiac injury measurements.

Results Rats with HF showed obvious histological changes including necrosis, elevated ventricular remodeling markers (MMP-9) levels, dysregulated ejection fraction (EF) value, and increased formation of oxidative stress. The radioimmunoassay of SOD shows that at the end of the study, the serum SOD in model group decreased by 32.86% (P < 0.05) compared with control. Results of MDA appeared reverse changes. MDA in model group increased by 33.62% (P < 0.05) compared with control, suggesting an oxidative stress response in HF. The two pathways lead to NADPH oxidases up-regulation which was believed to cause oxidative stress, Nox2 and Nox4 (subtypes of NADPH oxidase) showed different patterns in this model. NOX2 showed no statistical significance compared to control. The Western blot of NADPHoxidase 4(NOX4) showed a 62.00% compensatory increase (P<0.05) in model group, and it had a positive linear correlation with MMP-9.

Conclusions In conclusion, the activation of NOX2 and NOX4 showed a distinct pattern in LAD-induced HF model. Oxidative stress and cardiac hypertrophy in this model were induced partly through the NOX4-MMP-9 pathways, but no evidence had showed the change in NOX2, suggesting a NOX4-mediated myocardial injury effects against heart failure, and NOX-4 can be used as potential drug targets for HF.

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