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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Resum

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.
Idioma originalEnglish
Pàgines (de-a)168-180
RevistaCardiovascular Research
Volum94
Número2
DOIs
Estat de la publicacióPublicada - 1 de maig 2012

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