title: Preserved recovery of cardiac function following ischemia-reperfusion in mice lacking SIRT3.
abstract: 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.
authors.affiliation: a Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Koentges
authors.affiliation: a Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Pfeil
authors.affiliation: a Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Meyer-Steenbuck
authors.affiliation: 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.
authors.forename: Achim
authors.initials: A
authors.lastname: Lother
authors.affiliation: c Institute for Clinical Chemistry and Laboratory Medicine, Freiburg University Hospital, Freiburg, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.affiliation: a Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Katja E
authors.initials: KE
authors.lastname: Odening
authors.affiliation: b Institute of Experimental and Clinical Pharmacology, and Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Hein
authors.affiliation: a Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: a Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Bugger
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D004734:Energy Metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000503:physiopathology*; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D056566:Sirtuin 3 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C525046:Sirt3 protein, mouse; D000255:Adenosine Triphosphate; D056566:Sirtuin 3
keywords: SIRT3; cardiac function; cœur; fonction cardiaque; heart; infarctus du myocarde; ischemia–reperfusion; ischémie reperfusion; mitochondria; mitochondrie; myocardial infarction; sirtuin; sirtuine