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NADPH oxidase inhibition ameliorates cardiac dysfunction in rabbits with heart failure

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Abstract

Increased NADPH oxidase activity is found in both experimental and clinical HF. Here, we investigated the effects and mechanisms of NADPH oxidase inhibition on cardiac function in rabbits with HF. HF was induced by combined volume and pressure overload. Rabbits with HF or sham operation were randomized to orally receive apocynin, an inhibitor of NADPH oxidase (15 mg per day) or placebo for 8 weeks. Echocardiography was performed to examine the cardiac function and structure of the rabbits. Cardiac fibrosis was evaluated by masson’s trichrome staining. The transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) expression were measured by real-time PCR. The expression of SERCA2a and phospholamban (PLB) was detected by reverse transcription-polymerase chain reaction and Western Blot. SERCA2a activity was evaluated by measuring the Pi liberated from ATP hydrolysis. Rabbits with HF exhibited cardiac dysfunction and fibrosis. These changes were associated with significant increases in myocardial NADPH oxidase activity and oxidative stress. Compared with sham-operated rabbits, the TGF-β, CTGF, MMP-2, and MMP-9 mRNA expression significantly increased, the expression of SERCA2a and PLB dramatically decreased, and the SERCA2a activity was lower in HF rabbits. Apocynin reduced NADPH oxidase activity and oxidative stress, decreased TGF-β, CTGF, MMP-2, and MMP-9 expression, attenuated cardiac fibrosis, increased SERCA2a and PLB expression, restored SERCA2a activity, and thereby ameliorated cardiac dysfunction. Thus, chronic NADPH oxidase inhibition ameliorated cardiac dysfunction by decreasing cardiac fibrosis and preserving SERCA2a expression and activity.

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Acknowledgments

The authors greatly appreciate Doctor Jinlin Chen for technical assistance. This work was supported by a grant from National Natural Science Foundation of China (No. 30700312).

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Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei province, 430060, People’s Republic of China

    Yu Liu, He Huang, Yanhong Tang, Haitao Li & Congxin Huang

  2. Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People’s Republic of China

    Yu Liu, He Huang, Yanhong Tang, Haitao Li & Congxin Huang

  3. Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China

    Wenfang Xia

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  1. Yu Liu
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  2. He Huang
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Correspondence to Congxin Huang.

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Yu Liu and He Huang contributed equally to this work.

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Liu, Y., Huang, H., Xia, W. et al. NADPH oxidase inhibition ameliorates cardiac dysfunction in rabbits with heart failure. Mol Cell Biochem 343, 143–153 (2010). https://doi.org/10.1007/s11010-010-0508-4

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