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Is Autophagy in Response to Ischemia and Reperfusion Protective or Detrimental for the Heart?

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Abstract

Autophagy is a catabolic process that degrades long-lived proteins and damaged organelles by sequestering them into double membrane structures termed “autophagosomes” and fusing them with lysosomes. Autophagy is active in the heart at baseline and further stimulated under stress conditions including starvation, ischemia/reperfusion, and heart failure. It plays an adaptive role in the heart at baseline, thereby maintaining cardiac structure and function and inhibiting age-related cardiac abnormalities. Autophagy is activated by ischemia and nutrient starvation in the heart through Sirt1-FoxO- and adenosine monophosphate (AMP)-activated protein kinase (AMPK)-dependent mechanisms, respectively. Activation of autophagy during ischemia is essential for cell survival and maintenance of cardiac function. Autophagy is strongly activated in the heart during reperfusion after ischemia. Activation of autophagy during reperfusion could be either protective or detrimental, depending on the experimental model. However, strong induction of autophagy accompanied by robust upregulation of Beclin1 could cause autophagic cell death, thereby proving to be detrimental. This review provides an overview regarding both protective and detrimental functions of autophagy in the heart and discusses possible applications of current knowledge to the treatment of heart disease.

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Acknowledgments

This work was supported in part by U.S. Public Health Service Grants HL59139, HL67724, HL69020, HL91469, HL102738, and AG27211, and by the Foundation of Leducq Transatlantic Network of Excellence.

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Authors and Affiliations

  1. Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Medical Science Building G-609, Newark, NJ, 07103, USA

    Sebastiano Sciarretta, Nirmala Hariharan, Yoshiya Monden, Daniela Zablocki & Junichi Sadoshima

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  1. Sebastiano Sciarretta
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  2. Nirmala Hariharan
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  3. Yoshiya Monden
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  4. Daniela Zablocki
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  5. Junichi Sadoshima
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Correspondence to Junichi Sadoshima.

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Sciarretta, S., Hariharan, N., Monden, Y. et al. Is Autophagy in Response to Ischemia and Reperfusion Protective or Detrimental for the Heart?. Pediatr Cardiol 32, 275–281 (2011). https://doi.org/10.1007/s00246-010-9855-x

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  • DOI: https://doi.org/10.1007/s00246-010-9855-x

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