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  • Acquired Diseases
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Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts

Gene Therapy volume 7, pages 1847–1852 (2000)Cite this article

Abstract

Acute rejection and graft arteriopathy in cardiac transplantation limit the long-term survival of recipients; these processes are enhanced by several cytokines and adhesion molecules. Nuclear factor-kappa B (NFκB) is critical in the transcription of multiple genes involved in inflammation and cell proliferation. To test the hypothesis that NFκB decoy can attenuate acute rejection and arteriopathy, we performed single intraluminal delivery of NFκB decoy into murine cardiac allografts using a hemagglutinating virus of Japan (HVJ)-artificial viral envelope (AVE)-liposome method. No decoy or scrambled decoy transfer was performed for control. Hearts were heterotopically transplanted from BALB/c to C3H/He mice (major mismatch group) and from DBA/2 to B10.D2 mice (minor mismatch group). Nontreated or scrambled decoy transfected allografts of the major mismatch group were acutely rejected, while NFκB decoy prolonged their survival. While severe cell infiltration and intimal thickening with enhancement of inflammatory factors were observed in untreated or scrambled decoy-treated allografts of minor mismatch group at day 28, NFκB decoy attenuated these changes. We conclude that NFκB is critically involved in the development of acute as well as chronic rejection of the transplanted hearts. NFκB decoy attenuates both acute rejection and graft arteriopathy by blocking the activation of several genes.

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Acknowledgements

This study was supported by grants from Grant-in-Aid from the Ministry of Education, Science and Culture, Grant-in-Aid from Ministry of Health and Welfare, Research Grant for Immunology, Allergy and Organ Transplant, Japan Heart Foundation Research Grant and Grant-in-Aid from the Kanae Foundation for Life and Socio-Medical Science. We would like to thank Midori Oike and Rie Shiohara for excellent technical assistance.

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Authors and Affiliations

  1. Department of Internal Medicine I, Shinshu University School of Medicine, Nagano, Japan

    J Suzuki & M Isobe

  2. Division of Gene Therapy Science, Faculty of Medicine, Osaka University, Osaka, Japan

    R Morishita & Y Kaneda

  3. Department of Surgery II Shinshu, University School of Medicine, Nagano, Japan

    J Amano

  4. Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan

    M Isobe

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  1. J Suzuki
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Suzuki, J., Morishita, R., Amano, J. et al. Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts. Gene Ther 7, 1847–1852 (2000). https://doi.org/10.1038/sj.gt.3301316

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  • DOI: https://doi.org/10.1038/sj.gt.3301316

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