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The potentials of distinct functions of autophagy to be targeted for attenuation of myocardial ischemia/reperfusion injury in preclinical studies: an up-to-date review

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Abstract

Despite remarkable advances in our knowledge about the function of autophagy in myocardial ischemia/reperfusion (I/R) injury, the debate continues over whether autophagy is protective or deleterious in cardiac I/R. Due to the complexity of autophagy signaling, autophagy can play a dual role in the pathological processes of myocardial I/R injury. Thus, more researches are needed to shed light on the complex roles of autophagy in cardioprotection for the future clinical development. Such researches can lead to the finding of new therapeutic strategies for improving cardiac I/R outcomes in patients. Several preclinical studies have targeted autophagy flux as a beneficial strategy against myocardial I/R injury. In this review, we aimed to discuss the complex contribution of autophagy in myocardial I/R injury, as well as the therapeutic agents that have been shown to be useful in reducing myocardial I/R injury by targeting autophagy. For this reason, we provided an updated summary of the data from in vivo, ex vivo, and in vitro experimental studies about the therapeutic agents that exert positive effects against myocardial I/R injury by modulating autophagy flux. By addressing these valuable studies, we try to provide a motivation for the promising hypothesis of “autophagy modulation as a therapeutic strategy against cardiac I/R” in the future clinical studies.

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Authors and Affiliations

  1. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Behnaz Mokhtari

  2. Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Behnaz Mokhtari & Reza Badalzadeh

  3. Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Behnaz Mokhtari & Reza Badalzadeh

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  1. Behnaz Mokhtari
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BM had the idea for the article. BM performed the literature search and data collecting, drafted the manuscript, and designed the figures and tables. RB edited the language and critically revised the manuscript. All gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Reza Badalzadeh.

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Key points

1. Higher or lower activity of autophagy may have harmful effects in the heart.

2. Excessive or insufficient autophagy flux is involved in myocardial I/R damage.

3. Modulation of autophagy is potential therapeutic target in myocardial I/R injury.

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Mokhtari, B., Badalzadeh, R. The potentials of distinct functions of autophagy to be targeted for attenuation of myocardial ischemia/reperfusion injury in preclinical studies: an up-to-date review. J Physiol Biochem 77, 377–404 (2021). https://doi.org/10.1007/s13105-021-00824-x

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  • DOI: https://doi.org/10.1007/s13105-021-00824-x

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