Title:The Role of Calcium Handling Mechanisms in Reperfusion Injury
Volume: 24
Issue: 34
Author(s): Konstantinos Pittas, Dimitrios A. Vrachatis*, Christos Angelidis, Styliani Tsoucala, Georgios Giannopoulos and Spyridon Deftereos
Affiliation:
- Department of Cardiology, ,Greece
Keywords:
Calcium, reperfusion injury, cardiovascular diseases, stroke, myocardial infarction, primary percutaneous coronary intervention.
Abstract: Cardiovascular diseases, such as stroke and myocardial infarction (MI) remain the major cause of
death and disability worldwide. However, the mortality of MI has declined dramatically over the past several
decades because of advances in medicines (thrombolytic agents, antiplatelet drugs, beta blockers, and angiotensin
converting enzyme inhibitors) and approaches to restore tissue perfusion (percutaneous coronary intervention and
cardiopulmonary bypass). Animal studies have been shown that these treatments have been effective in reducing
acute myocardial ischemic injury and limiting MI size. The paradox is that the process of reperfusion can itself
amplify cell injury and death, known as myocardial ischemia-reperfusion injury (I/R). Intensive research has
uncovered several complex mechanisms of cardiomyocyte damage after reperfusion,and potential therapeutic
targets for preventing I/R. Importantly, it is now recognized that excessive elevation of intracellular and mitochondrial
Ca2+during reperfusion predisposes the cells to hypercontracture, proteolysis and mitochondrial failure
and eventually to necrotic or apoptotic death. These enormous alterations in cytosolic Ca2+ levels are induced by
the Ca2+ channels of the sarcolemma(L-Type Ca2+channels, sodium/calcium exchanger), the endoplasmic/
sarcoplasmic reticulum (SERCA ATPase) and ryanodine receptors, SOCE(store-operated calcium entry),
lysosomes and others, which are modified by I/R injury. The overall goal of this review is to describe the different
pathways that lead to I/R injury via Ca2+ overload, focus on recent discoveries and highlight prospects for
therapeutic strategies for clinical benefit.
