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Apoptosis in congestive heart failure induced by viral myocarditis in mice

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Summary

It has recently been speculated that progressive deterioration of left ventricular function in chronic heart failure is due to the ongoing loss of viable cardiac myocytes. However, as there is little direct evidence of significant apoptosis contributing to the pathogenesis in cardiac myocytes in vivo, the significance of apoptosis in heart failure remains to be clarified. We investigated the role of apoptosis in heart failure induced by encephalomyocarditis virus myocarditis. DBA/2 mice were inoculated with the virus (day 0), then killed, and their hearts were extracted 3 to 28 days later. Internucleosomal DNA fragmentation, chromatin binding dye staining, and in situ terminal transferase deoxyuridine triphosphate (dUTP) endlabeling were used to detect apoptosis. Internucleosomal DNA fragmentation (DNA ladder) was clearly demonstrated on days 5 to 14 in the virusinfected hearts when myocardial necrosis and infiltration of mononuclear cells were prominent in the hearts. Apoptotic cells demonstrated morphological changes typical of apoptosis (condensation of chromatin and nuclear fragmentation). Both Fas antigen and Fas ligand immunoreactivity were detected in the infiltrating mononuclear cells. The in situ terminal transferase dUTP end-labeling method demonstrated condensed nuclei of infiltrating mononuclear cells on day 7. However, nuclei of cardiac myocytes surrounded by the cellular infiltration were absent. The main source of apoptotic cells in the heart in mice with viral myocarditis appeared to be the infiltrating mononuclear cells.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Kawaracho, Shogoin, Sakyo-ku, 606-8397, Kyoto, Japan

    Takehiko Yamada, Akira Matsumori, Wei Zhong Wang, Naohiro Ohashi & Shigetake Sasayama

  2. Department of Anatomy and Developmental Biology, Kyoto University Graduate School of Medicine, 54 Kawaracho, Shogoin, Sakyo-ku, 606-8397, Kyoto, Japan

    Wei Zhong Wang & Kohei Shiota

Authors
  1. Takehiko Yamada
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  2. Akira Matsumori
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  3. Wei Zhong Wang
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  4. Naohiro Ohashi
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  5. Kohei Shiota
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  6. Shigetake Sasayama
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This work was supported in part by a grant-in-aid for General Scientific Research, and a research grant from the Ministry of Health and Welfare, Japan.

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Yamada, T., Matsumori, A., Wang, W.Z. et al. Apoptosis in congestive heart failure induced by viral myocarditis in mice. Heart Vessels 14, 29–37 (1999). https://doi.org/10.1007/BF02481740

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  • DOI: https://doi.org/10.1007/BF02481740

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