Calcium-mediated cell death during myocardial reperfusion

David Garcia-Dorado, Marisol Ruiz-Meana, Javier Inserte, Antonio Rodriguez-Sinovas, Hans Michael Piper

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162 Citations (Scopus)

Abstract

Reperfusion may induce additional cell death in patients with acute myocardial infarction receiving primary angioplasty or thrombolysis. Altered intracellular Ca 2+ handling was initially considered an essential mechanism of reperfusion-induced cardiomyocyte death. However, more recent studies have demonstrated the importance of Ca 2+-independent mechanisms that converge on mitochondrial permeability transition (MPT) and are shared by cardiomyocytes and other cell types. This article analyses the importance of Ca 2+-dependent cell death in light of these new observations. Altered Ca 2+ handling includes increased cytosolic Ca 2+ levels, leading to activation of calpain-mediated proteolysis and sarcoplasmic reticulum-driven oscillations; this can induce hypercontracture, but also MPT due to the privileged Ca 2+ transfer between sarcoplasmic reticulum and mitochondria through cytosolic Ca 2+ microdomains. In the opposite direction, permeability transition can worsen altered Ca 2+ handling and favour hypercontracture. Ca 2+ appears to play an important role in cell death during the initial minutes of reperfusion, particularly after brief periods of ischaemia. Developing effective and safe treatments to prevent Ca 2+-mediated cardiomyocyte death in patients with transient ischaemia, by targeting Ca 2+ influx, intracellular Ca 2+ handling, or Ca 2+-induced cell death effectors, is an unmet challenge with important therapeutic implications and large potential clinical impact. © 2011 The Author.
Original languageEnglish
Pages (from-to)168-180
JournalCardiovascular Research
Volume94
Issue number2
DOIs
Publication statusPublished - 1 May 2012

Keywords

  • Calpain
  • Mitochondria
  • Myocardial infarction
  • Reperfusion injury

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    Garcia-Dorado, D., Ruiz-Meana, M., Inserte, J., Rodriguez-Sinovas, A., & Piper, H. M. (2012). Calcium-mediated cell death during myocardial reperfusion. Cardiovascular Research, 94(2), 168-180. https://doi.org/10.1093/cvr/cvs116