Roles of mitochondrial dynamics modulators in cardiac ischaemia/reperfusion injury

J Cell Mol Med. 2017 Nov;21(11):2643-2653. doi: 10.1111/jcmm.13330. Epub 2017 Sep 22.

Abstract

The current therapeutic strategy for the management of acute myocardial infarction (AMI) is to return blood flow into the occluded coronary artery of the heart, a process defined as reperfusion. However, reperfusion itself can increase mortality rates in AMI patients because of cardiac tissue damage and dysfunction, which is termed 'ischaemia/reperfusion (I/R) injury'. Mitochondria play an important role in myocardial I/R injury as disturbance of mitochondrial dynamics, especially excessive mitochondrial fission, is a predominant cause of cardiac dysfunction. Therefore, pharmacological intervention and therapeutic strategies which modulate the mitochondrial dynamics balance during I/R injury could exert great beneficial effects to the I/R heart. This review comprehensively summarizes and discusses the effects of mitochondrial fission inhibitors as well as mitochondrial fusion promoters on cardiac and mitochondrial function during myocardial I/R injury. The comparison of the effects of both compounds given at different time-points during the course of I/R injury (i.e. prior to ischaemia, during ischaemia and at the reperfusion period) are also summarized and discussed. Finally, this review also details important information which may contribute to clinical practices using these drugs to improve the quality of life in AMI patients.

Keywords: heart; ischaemia reperfusion injury; mitochondrial dynamics; mitochondrial fission; mitochondrial fusion.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology*
  • Cell Line
  • Disease Models, Animal
  • GTP Phosphohydrolases / pharmacology
  • Humans
  • Hydrazones / pharmacology
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Mitochondrial Dynamics / drug effects*
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Peptide Fragments / pharmacology
  • Quinazolinones / pharmacology
  • Tacrolimus / pharmacology
  • Ventricular Function, Left / drug effects

Substances

  • 3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone
  • Cardiotonic Agents
  • Hydrazones
  • N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide
  • P110 peptide
  • Peptide Fragments
  • Quinazolinones
  • GTP Phosphohydrolases
  • Tacrolimus