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The Effect of c-fos on Acute Myocardial Infarction and the Significance of Metoprolol Intervention in a Rat Model

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Abstract

Over-expression of c-fos may play a role in some diseases. Research pertaining to the expression of c-fos in acute myocardial ınfarction (AMI) is rare, and the detailed role of c-fos in AMI has not been reported. Therefore, the purpose of this project was to elucidate the detailed effect of c-fos on AMI rats and evaluate the effect of a metoprolol intervention. An AMI rat model was established for the purposes of this study. The expression of c-fos in AMI was evaluated via immunohistochemical analysis and in situ hybridization. Simultaneously, we investigated the effect of c-fos on AMI rats via medicinal treatment with c-fos monoclonal antibody, isoproterenol, and metoprolol. Positive c-Fos protein expression and c-fos mRNA expression in cardiomyocytes were increased at 1, 3, 7, and 10 days after ligation in AMI rats compared with a sham-operated group. Peak expression occurred at 3 days after ligation. The weight percentage fraction of infarct size was decreased in rats treated with c-fos monoclonal antibody compared with the control normal saline treatment group. The weight percentage fraction of infarction size was increased after c-fos was increased via the administration of isoproterenol. c-Fos protein expression and the infarct size in rats treated with metoprolol were also decreased compared with the control normal saline treatment group. The results showed that c-fos expression rapidly increased after coronary ligation; c-fos plays an important role in myocardial lesions and is likely to be involved in the pathogenesis of AMI as well. Metoprolol can inhibit the expression of c-fos and has a positive therapeutic effect on rats after AMI; the involvement effect of metoprolol on myocardial infarction might be correlated with its effect on the inhibition of c-fos.

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References

  1. Jin, S. P., Kim, J. H., Kim, M. A., et al. (2007). Prognostic significance of loss of c-Fos protein in gastric carcinoma. Pathology and Oncology Research, 13, 284–289.

    Article  PubMed  CAS  Google Scholar 

  2. Zhou, H., Gao, J., Lu, Z. Y., et al. (2007). Role of c-Fos/JunD in protecting stress-induced cell death. Cell Proliferation, 40, 431–444.

    Article  PubMed  CAS  Google Scholar 

  3. Zhang, S., He, B., Goldstein, S., et al. (2011). Changes in adiponectin expression in acute myocardial infarction rats and the significance of bisoprolol intervention. Canadian Journal of Physiology and Pharmacology, 89, 109–115.

    Article  PubMed  CAS  Google Scholar 

  4. Dalla Libera, L., Ravara, B., Gobbo, V., et al. (2005). Skeletal muscle myofibrillar protein oxidation in heart failure and the protective effect of Carvedilol. Journal of Molecular and Cellular Cardiology, 38, 803–807.

    Article  PubMed  CAS  Google Scholar 

  5. Watanabe, K., Ohta, Y., Inoue, M., et al. (2001). Bisoprolol improves survival in rats with heart failure. Journal of Cardiovascular Pharmacology, 38(Suppl 1), S55–S58.

    Article  PubMed  CAS  Google Scholar 

  6. Zhang, S., He, B., Goldstein, S., et al. (2010). The expression and significance of proto-oncogene c-fos in viral myocarditis. Virology Journal, 7, 285.

    Article  PubMed  Google Scholar 

  7. Verma, I. M., & Sassone-Corsi, P. (1987). Proto-oncogene fos: Complex but versatile regulation. Cell, 51, 513–514.

    Article  PubMed  CAS  Google Scholar 

  8. Miller, A. D., Curran, T., & Verma, I. M. (1984). c-Fos protein can induce cellular transformation: A novel mechanism of activation of a cellular oncogene. Cell, 36, 51–60.

    Article  PubMed  CAS  Google Scholar 

  9. Barker, P. E., Rabin, M., Watson, M., et al. (1984). Human c-fos oncogene mapped within chromosomal region 14q21—q31. Proceedings of the Natural Academy of Sciences USA, 81, 5826–5830.

    Article  CAS  Google Scholar 

  10. Sng, J. C., Taniura, H., & Yoneda, Y. (2004). A tale of early response genes. Biological and Pharmaceutical Bulletin, 27, 606–612.

    Article  PubMed  CAS  Google Scholar 

  11. Herdegen, T., & Waetzig, V. (2001). AP-1 proteins in the adult brain: facts and fiction about effectors of neuroprotection and neurodegeneration. Oncogene, 20, 2424–2437.

    Article  PubMed  CAS  Google Scholar 

  12. Chiu, R., Boyle, W. J., Meek, J., et al. (1988). The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell, 54, 541–552.

    Article  PubMed  CAS  Google Scholar 

  13. Patel, K. P., Zhang, K., Kenney, M. J., et al. (2000). Neuronal expression of Fos protein in the hypothalamus of rats with heart failure. Brain Research, 865, 27–34.

    Article  PubMed  CAS  Google Scholar 

  14. Itoh, H., Yagi, M., Fushida, S., et al. (2000). Activation of immediate early gene, c-fos, and c-jun in the rat small intestine after ischemia/reperfusion. Transplantation, 69, 598–604.

    Article  PubMed  CAS  Google Scholar 

  15. Sakai, H., Urasawa, K., Oyama, N., et al. (2007). Induction of c-fos mRNA expression by pure pressure overload in cultured cardiac myocytes. International Heart Journal, 48, 359–367.

    Article  PubMed  CAS  Google Scholar 

  16. Schneider, H. J., Rossner, S., Pfeiffer, D., et al. (2008). d-ribose improves cardiac contractility and hemodynamics, and reduces expression of c-fos in the hippocampus during sustained slow ventricular tachycardia in rats. International Journal of Cardiology, 125, 49–56.

    Article  PubMed  Google Scholar 

  17. Lavezzi, A. M., Milei, J., Grana, D. R., et al. (2003). Expression of c-fos, p53 and PCNA in the unstable atherosclerotic carotid plaque. International Journal of Cardiology, 92, 59–63.

    Article  PubMed  Google Scholar 

  18. Nelson, D. P., Wechsler, S. B., Miura, T., et al. (2002). Myocardial immediate early gene activation after cardiopulmonary bypass with cardiac ischemia-reperfusion. Annals of Thoracic Surgery, 73, 156–162.

    Article  PubMed  Google Scholar 

  19. Gidh-Jain, M., Huang, B., Jain, P., et al. (1998). Alterations in cardiac gene expression during ventricular remodeling following experimental myocardial infarction. Journal of Molecular and Cellular Cardiology, 30, 627–637.

    Article  PubMed  CAS  Google Scholar 

  20. Larsen, T. H., Skar, R., Frotjold, E. K., et al. (1998). Regional activation of the immediate-early response gene c-fos in infarcted rat hearts. International Journal of Experimental Pathology, 79, 163–172.

    Article  PubMed  CAS  Google Scholar 

  21. Ueyama, T., Sakoda, T., Kawashima, S., et al. (1997). Activated RhoA stimulates c-fos gene expression in myocardial cells. Circulation Research, 81, 672–678.

    Article  PubMed  CAS  Google Scholar 

  22. Barka, T., van der Noen, H., & Shaw, P. A. (1987). Proto-oncogene fos (c-fos) expression in the heart. Oncogene, 1, 439–443.

    PubMed  CAS  Google Scholar 

  23. Takeshita, A., Shinoda, H., Nakabayashi, Y., et al. (2005). Sphingosine 1-phosphate acts as a signal molecule in ceramide signal transduction of TNF-alpha-induced activator protein-1 in osteoblastic cell line MC3T3-E1 cells. Journal of Oral Science, 47, 43–51.

    Article  PubMed  CAS  Google Scholar 

  24. Emch, G. S., Hermann, G. E., & Rogers, R. C. (2001). TNF-alpha-induced c-Fos generation in the nucleus of the solitary tract is blocked by NBQX and MK-801. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 281, R1394–R1400.

    PubMed  CAS  Google Scholar 

  25. Haliday, E. M., Ramesha, C. S., & Ringold, G. (1991). TNF induces c-fos via a novel pathway requiring conversion of arachidonic acid to a lipoxygenase metabolite. EMBO Journal, 10, 109–115.

    PubMed  CAS  Google Scholar 

  26. Ono, H., Ichiki, T., Fukuyama, K., et al. (2004). cAMP-response element-binding protein mediates tumor necrosis factor-alpha-induced vascular smooth muscle cell migration. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 1634–1639.

    Article  PubMed  CAS  Google Scholar 

  27. Lurje, L., Wennerblom, B., Tygesen, H., et al. (1997). Heart rate variability after acute myocardial infarction in patients treated with atenolol and metoprolol. International Journal of Cardiology, 60, 157–164.

    Article  PubMed  CAS  Google Scholar 

  28. Ibanez, B., Cimmino, G., Prat-Gonzalez, S., et al. (2011). The cardioprotection granted by metoprolol is restricted to its administration prior to coronary reperfusion. International Journal of Cardiology, 147, 428–432.

    Article  PubMed  Google Scholar 

  29. Herlitz, J., Hjalmarson, A., Swedberg, K., et al. (1984). Relationship between infarct size and incidence of severe ventricular arrhythmias in a double-blind trial with metoprolol in acute myocardial infarction. International Journal of Cardiology, 6, 47–60.

    Article  PubMed  CAS  Google Scholar 

  30. Yan, S. H., Hu, H. S., Wang, X. L., et al. (2007). Effects of prolonged metoprolol treatment on neural remodeling and inducible ventricular arrhythmias after myocardial infarction in rabbits. International Journal of Cardiology, 117, 317–322.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiovascular Diseases, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China

    Song Zhang & Yigang Li

  2. Department of Cardiology, Washington Hospital Center, 110 Irving Street, Washington, DC, 20010, USA

    Steven Goldstein & George Ruiz

  3. Department of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China

    Junbo Ge

  4. Department of Cardiovascular Diseases, Eastern District of Renji Hospital, Shanghai Jiaotong University, 1630 Dongfang Road, Shanghai, 200127, China

    Ben He

  5. Emergency Department, People’s Hospital of Zhejiang, 158 Shangtang Road, Hangzhou, 310014, Zhejiang, China

    Meiqi Zhang

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  1. Song Zhang
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  2. Meiqi Zhang
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  4. Yigang Li
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  5. Junbo Ge
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Correspondence to Yigang Li.

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Zhang, S., Zhang, M., Goldstein, S. et al. The Effect of c-fos on Acute Myocardial Infarction and the Significance of Metoprolol Intervention in a Rat Model. Cell Biochem Biophys 65, 249–255 (2013). https://doi.org/10.1007/s12013-012-9428-0

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  • DOI: https://doi.org/10.1007/s12013-012-9428-0

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