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Anti-apoptosis in nonmyocytes and pro-autophagy in cardiomyocytes: two strategies against postinfarction heart failure through regulation of cell death/degeneration

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Abstract

Anti-apoptotic therapy for cardiomyocytes could be an effective strategy for preventing or treating heart failure. Notably, however, morphological evidence definitively demonstrating cardiomyocyte apoptosis has been very rare in actual heart diseases such as acute myocardial infarction and heart failure. By contrast, within the postinfarction heart, interstitial noncardiomyocytes such as granulation tissue cells do die via apoptosis to form scar tissue. Blockade of this apoptosis improves survival and mitigates ventricular remodeling and dysfunction during the chronic stage. Possible mechanisms to explain this benefit might be preservation of infarcted wall thickness and preservation of myofibroblasts, which could promote infarct shrinkage; both would reduce wall stress through Laplace’s law. On the other hand, autophagy is an intracellular degradation mechanism that compensates for energy insufficiency by digesting and recycling intracellular components, and is often observed in cardiomyocytes within failing hearts with various origins including postinfarction. Starvation strongly induces and activates autophagic degeneration within cardiomyocytes. When that activation is inhibited, the starved animals suffer from heart failure. Promoting autophagy through caloric restriction or several reagents not only reduces the acute infarct size but also mitigates postinfarction cardiac remodeling and dysfunction during chronic stages. Moreover, augmenting autophagy by the treatment with resveratrol or exercise can bring about reverse remodeling in failing hearts with a large old myocardial infarction. In conclusion, we propose two strategies for managing postinfarction heart failure through control of cell death/degeneration: (1) anti-apoptosis in granulation tissue noncardiomyocytes; and (2) pro-autophagy in salvaged cardiomyocytes.

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Acknowledgments

This study was supported in part by Research Grant from Asahi University and Grant-in-Aid for Scientific Research (16K09509) from the Ministry of Educational, Cultural, Sports, Science and Technology of Japan. The authors thank Yasuaki Hotta, Akiko Niwa, Rieko Hori, and Norie Soga at Asahi University for their technical and secretarial assistance.

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Authors and Affiliations

  1. Department of Internal Medicine, Asahi University School of Dentistry, 1851 Hozumi, Mizuho, 501-0296, Japan

    Genzou Takemura, Hideshi Okada, Nagisa Miyazaki & Akiko Tsujimoto

  2. Department of Cardiology, Gifu University School of Medicine, Gifu, Japan

    Genzou Takemura, Hiromitsu Kanamori, Hideshi Okada, Takatomo Watanabe, Akiko Tsujimoto, Kazuko Goto & Rumi Maruyama

  3. Department of Emergency and Disaster Medicine, Gifu University School of Medicine, Gifu, Japan

    Hideshi Okada

  4. Department of Food and Nutrition, Sonoda Women’s University, Amagasaki, Japan

    Takako Fujiwara

  5. Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan

    Hisayoshi Fujiwara

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  1. Genzou Takemura
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  2. Hiromitsu Kanamori
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Correspondence to Genzou Takemura.

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Takemura, G., Kanamori, H., Okada, H. et al. Anti-apoptosis in nonmyocytes and pro-autophagy in cardiomyocytes: two strategies against postinfarction heart failure through regulation of cell death/degeneration. Heart Fail Rev 23, 759–772 (2018). https://doi.org/10.1007/s10741-018-9708-x

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