Ischemia reperfusion (I/R) injury is a common event following myocardial infarction (MI) resulting in excessive oxidative stress, calcium overload, inflammation, and cardiomyocyte death. Mitochondrial homeostasis including their dynamics are imbalanced in cardiac I/R injury in favor of increased mitochondrial fission. Inhibition of mitochondrial fission prior to I/R injury is protective and improves cardiac function following MI. Clinically, patients with MI often receive treatment following initiation of the ischemic event. Thus, treatments with more realistic timing would have better translational value and are important to research. In a recent study published in Clinical Science, Maneechote et al. [Clin. Sci. (2018) 132, 1669–1683] examined the effect of inhibiting mitochondrial fission using the mitochondrial division inhibitor (Mdivi-1) at different time points, pre-ischemia, during-ischemia, and upon onset of reperfusion, in a rat cardiac I/R model. The findings showed the greatest cardiac function improvement with pre-ischemia treatment along with decreased mitochondrial fragmentation and increased mitochondrial function. Mdivi-1 given during ischemia and at onset of reperfusion also improved cardiac function, but to a lesser extent than pre-ischemia intervention. Maneechote et al. postulated that the LV protection by Mdivi-1 in cardiac I/R could be due to an improvement in mitochondrial dysfunction through attenuating excessive mitochondrial fission which then reduces apoptotic myocytes. Their findings provide new insights into future treatment of patients suffering acute MI which could consider targetting the excessive mitochondrial fission during cardiac ischemia or at onset of reperfusion. Here, we will further discuss the background of the study, potential molecular mechanisms of mitochondrial fission, consequences of the fission, and future research directions.
Inhibition of mitochondrial fission as a novel therapeutic strategy to reduce mortality upon myocardial infarction
Hannah A. Cooper, Satoru Eguchi; Inhibition of mitochondrial fission as a novel therapeutic strategy to reduce mortality upon myocardial infarction. Clin Sci (Lond) 31 October 2018; 132 (20): 2163–2167. doi: https://doi.org/10.1042/CS20180671
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