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Mechanistic Role of mPTP in Ischemia-Reperfusion Injury

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Mitochondrial Dynamics in Cardiovascular Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 982))

Abstract

Acute myocardial infarction (MI) is a major cause of death and disability worldwide. The treatment of choice for reducing ischemic injury and limiting infarct size (IS) in patients with ST-segment elevation MI (STEMI) is timely and effective myocardial reperfusion via primary percutaneous coronary intervention (PCI). However, myocardial reperfusion itself may induce further cardiomyocyte death, a phenomenon known as reperfusion injury (RI). The opening of a large pore in the mitochondrial membrane, namely, the mitochondrial permeability transition pore (mPTP), is widely recognized as the final step of RI and is responsible for mitochondrial and cardiomyocyte death. Although myocardial reperfusion interventions continue to improve, there remain no effective therapies for preventing RI due to incomplete knowledge regarding RI components and mechanisms and to premature translations of findings from animals to humans. In the last year, increasing amounts of data describing mPTP components, structure, regulation and function have surfaced. These data may be crucial for gaining a better understanding of RI genesis and for planning future trials evaluating new cardioprotective strategies. In this chapter, we review the role of the mPTP in RI pathophysiology and report on recent studies investigating its structure and components. Finally, we provide a brief overview of principal cardioprotective strategies and their pitfalls.

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Acknowledgements

PP is grateful to Camilla degli Scrovegni for continuous support. PP is supported by the Italian Ministry of Education, University and Research (COFIN no. 20129JLHSY_002, FIRB no. RBAP11FXBC_002, and Futuro in Ricerca no. RBFR10EGVP_001), the Italian Cystic Fibrosis Research Foundation (19/2014) and Telethon (GGP15219/B). PP and CG are supported by local funds from the University of Ferrara and the Italian Ministry of Health, as well as by the Italian Association for Cancer Research (AIRC: IG- 18624 and MFAG-13521).

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  1. Department of Morphology, Surgery and Experimental Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Ferrara, Italy

    Giampaolo Morciano, Massimo Bonora, Carlotta Giorgi & Paolo Pinton

  2. Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy

    Giampaolo Morciano, Massimo Bonora, Carlotta Giorgi & Paolo Pinton

  3. Cardiovascular Institute, Azienda Ospedaliera Universitaria di Ferrara, Ferrara, Italy

    Gianluca Campo

  4. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Giorgio Aquila & Paola Rizzo

  5. Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland

    Mariusz R. Wieckowski

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  1. Giampaolo Morciano
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  8. Paolo Pinton
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Correspondence to Paolo Pinton .

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  1. Dept. of Biomedical Advanced Sciences, Federico II University, Naples, Italy

    Gaetano Santulli

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Morciano, G. et al. (2017). Mechanistic Role of mPTP in Ischemia-Reperfusion Injury. In: Santulli, G. (eds) Mitochondrial Dynamics in Cardiovascular Medicine. Advances in Experimental Medicine and Biology, vol 982. Springer, Cham. https://doi.org/10.1007/978-3-319-55330-6_9

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