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.

Mechanistic role of mPTP in ischemia-reperfusion injury

MORCIANO, Giampaolo;BONORA, Massimo;CAMPO, Gianluca Calogero;AQUILA, Giorgio;RIZZO, Paola;GIORGI, Carlotta;PINTON, Paolo
2017

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.
2017
978-3-319-55329-0
978-3-319-55330-6
Apoptosis; Cardiovascular medicine; Ischemia-reperfusion injury; Mitochondria; mPTP; Medicine (all); Biochemistry, Genetics and Molecular Biology (all)
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2372783
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 84
  • ???jsp.display-item.citation.isi??? 83
social impact