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Journal Articles Current Medicinal Chemistry Year : 2009

Inhibition of mitochondrial membrane permeability as a putative pharmacological target for cardioprotection.

Abstract

Myocardial ischemia-reperfusion injury is a major cause of morbidity and mortality in developed countries. To date, the only treatment of complete ischemia is to restore blood flow; thus the search for new cardioprotective approaches is absolutely necessary to reduce the mortality associated with myocardial ischemia. Ischemia has long been considered to result in necrotic tissue damage but the reduction in oxygen supply can also lead to apoptosis. Therefore, in the last few years, mitochondria have become the subject of growing interest in myocardial ischemia-reperfusion since they are strongly involved in the regulation of the apoptotic process. Indeed, during ischemia-reperfusion, pathological signals converge in the mitochondria to induce permeabilization of the mitochondrial membrane. Two classes of mechanisms, which are not mutually exclusive, emerged to explain mitochondrial membrane permeabilization. The first occurs via a non-specific channel known as the mitochondrial permeability transition pore (mPTP) in the inner and the outer membranes causing disruption of the impermeability of the inner membrane, and ultimately complete inhibition of mitochondrial function. The second mechanism, involving only the outer membrane, induces the release of cell death effectors. Thus, drugs able to block or to limit mitochondrial membrane permeabilization may be cytoprotective during ischemia-reperfusion. The objective of this review is to examine the pharmacological strategies capable of inhibiting mitochondrial membrane permeabilization induced by myocardial ischemia-reperfusion.
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Dates and versions

inserm-00433929 , version 1 (15-04-2010)

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  • HAL Id : inserm-00433929 , version 1
  • PUBMED : 19835566

Cite

Didier Morin, Rana Assaly, Stéphanie Paradis, Alain Berdeaux. Inhibition of mitochondrial membrane permeability as a putative pharmacological target for cardioprotection.: mitochondrial membrane permeability, a pharmacological target for cardioprotection. Current Medicinal Chemistry, 2009, 16 (33), pp.4382-98. ⟨inserm-00433929⟩

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