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Can J Physiol Pharmacol. 2016 Jan;94(1):72-80. doi: 10.1139/cjpp-2015-0152. Epub 2015 Jul 19.

Preserved recovery of cardiac function following ischemia-reperfusion in mice lacking SIRT3.

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a Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
b Institute of Experimental and Clinical Pharmacology, and Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany.
c Institute for Clinical Chemistry and Laboratory Medicine, Freiburg University Hospital, Freiburg, Germany.


Lack of the mitochondrial deacetylase sirtuin 3 (SIRT3) impairs mitochondrial function and increases the susceptibility to induction of the mitochondrial permeability transition pore. Because these alterations contribute to myocardial ischemia-reperfusion (IR) injury, we hypothesized that SIRT3 deficiency may increase cardiac injury following myocardial IR. Hearts of 10-week-old mice were perfused in the isolated working mode and subjected to 17.5 min of global no-flow ischemia, followed by 30 min of reperfusion. Measurements before ischemia revealed a decrease in cardiac power (-20%) and rate pressure product (-15%) in SIRT3(-/-) mice. Mitochondrial state 3 respiration (-15%), ATP synthesis (-39%), and ATP/O ratios (-29%) were decreased in hearts of SIRT3(-/-) mice. However, percent recovery of cardiac power (WT 94% ± 9%; SIRT3(-/-) 89% ± 9%) and rate pressure product (WT 89% ± 16%; SIRT3(-/-) 96% ± 3%) following IR was similar in both groups. Myocardial infarct size was not increased in SIRT3(-/-) mice following permanent ligation of the left anterior descending coronary artery (LAD). Left ventricular pressure and dP/dtmax, and mitochondrial respiration and ATP synthesis were not different between groups following LAD ligation. Thus, despite pre-existing defects in cardiac function and mitochondrial respiratory capacity in SIRT3(-/-) mice, SIRT3 deficiency does not additionally impair cardiac function following IR or following myocardial infarction.


SIRT3; cardiac function; cœur; fonction cardiaque; heart; infarctus du myocarde; ischemia–reperfusion; ischémie reperfusion; mitochondria; mitochondrie; myocardial infarction; sirtuin; sirtuine

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