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

作者:Takemura Genzou; Kanamori Hiromitsu; Okada Hideshi; Miyazaki Nagisa; Watanabe Takatomo; Tsujimoto Akiko; Goto Kazuko; Maruyama Rumi; Fujiwara Takako; Fujiwara Hisayoshi
来源:Heart Failure Reviews, 2018, 23(5): 759-772.
DOI:10.1007/s10741-018-9708-x

摘要

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.

  • 出版日期2018-9