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Inhibition of MAPK signaling by eNOS gene transfer improves ventricular remodeling after myocardial infarction through reduction of inflammation

Molecular Biology Reports volume 37, pages 3067–3072 (2010)Cite this article

Abstract

Endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) may play an important role in attenuating cardiac remodeling and apoptosis after myocardial infarction. However, the anti-inflammation effects of eNOS in infarcted myocardium and the role of MAPK signaling in eNOS/NO mediated cardiac remodeling have not yet been elucidated. Adenovirus carrying Human eNOS gene was delivered locally into heart 4 days prior to induction of myocardial infarction (MI) by left anterior descending coronary artery ligation. Monocyte/macrophage infiltration was detected by ED-1 immunohistochemistry. Western blot was employed to examine the activation of MAPK. eNOS gene transfer significantly reduced myocardial infarct size and improved cardiac contractility as well as left ventricle (LV) diastolic function at 7 days after MI. In addition, eNOS gene transfer decreased monocyte/macrophage infiltration in the infarct region of the heart. Phosphorylation of MAPK after MI were also dramatically reduced by eNOS gene transfer. All the protective effects of eNOS were blocked by N(ω)-nitro-l-arginine methyl ester (L-NAME) administration, indicating a NO-mediated event. These results demonstrate that the eNOS/NO system provides cardiac protection after MI injury through inhibition of inflammation and suppression of MAPK signaling.

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Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu, People’s Republic of China

    Lei-Lei Chen, Tie Bin Zhu, Jun Huang, Lian Sheng Wang, Ke Jiang Cao & Zhi Jian Yang

  2. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425-2211, USA

    Hang Yin

Authors
  1. Lei-Lei Chen
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  2. Tie Bin Zhu
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  3. Hang Yin
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  4. Jun Huang
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  5. Lian Sheng Wang
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  6. Ke Jiang Cao
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  7. Zhi Jian Yang
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Correspondence to Jun Huang.

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Lei Lei Chen and Tie Bin Zhu have contributed equally to this article.

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Chen, LL., Zhu, T.B., Yin, H. et al. Inhibition of MAPK signaling by eNOS gene transfer improves ventricular remodeling after myocardial infarction through reduction of inflammation. Mol Biol Rep 37, 3067–3072 (2010). https://doi.org/10.1007/s11033-009-9879-6

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  • DOI: https://doi.org/10.1007/s11033-009-9879-6

Keywords

  • Endothelial nitric oxide synthase
  • Myocardial infarction
  • Remodeling
  • MAPK