Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie Mitochondrial dynamics as an underlying mechanism involved in aerobic exercise training-induced cardioprotection against ischemia-reperfusion injury Reza Ghahremani a,b , Arsalan Damirchi b, ⁎ , Iraj Salehi a , Alireza Komaki a , Fabio Esposito c,d a Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran b Department of Exercise Physiology, Faculty of Sport Sciences, University of Guilan, Rasht, Iran c Department of Biomedical Sciences for Health, Universita degli Studi di Milano, Milan, Italy d IRCCS Galeazzi Orthopedic Institute, Milan, Italy ARTICLE INFO Keywords: Ischemia-reperfusion Aerobic training Mitochondrial dynamics Cardioprotection ABSTRACT Aims: Ischemia-reperfusion injury is one of the most common cardiac disorders leading to irreversible heart damage. Many underlying mechanisms seem to be involved, among which mitochondrial dysfunction. Since physical training has a beneficial effect on mitochondrial dynamics (fusion and fission), it may have a cardio- protective effect against IR injury also via mitochondrial pathways. This study investigates the protective role of aerobic training against cardiac IR injury and the mitochondrial dynamics as a possible mechanism. Main methods: Thirty-two male Wistar rats (8-week old) were divided into a control, sham, control + IR, and training + IR groups (8 rats each). Training group was exercised aerobically on a treadmill for 8 weeks (5 days/ week). After 8 weeks, anesthetized rats underwent a left thoracotomy (sham, control + IR, and training + IR groups) to access the left anterior descending coronary artery, which was occluded by a silk suture for 30 min and released for 90 min of reperfusion (IR groups). Triphenyltetrazolium chloride staining was used to determine the infarct size. The gene expression of mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and dynamin-related protein 1 (Drp1) was evaluated by RT-PCR. A one-way ANOVA was used for statistical analysis with the significance level set at P ≤ 0.05. Key findings: Cardiac infarct size was smaller In training + IR group (20.24 ± 5.7%) than in control + IR (35.9 ± 2.3%; P ≤ 0.05). Training + IR showed higher expression of Mfn1 and Mfn2 (P ≤ 0.05). Conversely, Drp1 expression was lower after training (P ≤ 0.05). Significance: Exercise-induced regulation of mitochondrial fusion and fission, leading to improvement of mi- tochondrial dynamics seems to be involved in the cardioprotection against IR injuries. 1. Introduction Among different disabilities, cardiac diseases are the main cause of morbidity and mortality around the world [23]. These diseases have high healthcare costs for humans and governments. Thus, development of strategies to prevent myocardial disorders is an important approach for physicians and healthcare professionals. As a preliminary patholo- gical event associated with coronary artery disease, ischemia-reperfu- sion (IR) injury is one of the most common cardiac disorders that may lead to irreversible heart damage [23]. Human epidemiological studies show that regular physical activity has some given cardiovascular benefits [16]. Furthermore, previous studies have indicated that physical exercise training, as a pre- conditioning factor, can be cardioprotective against ischemia-reperfu- sion injury [7,11,23,28]. An altered glycolytic flux, impaired nitric oxide signaling, reduced sarcolemmal and mitochondrial ATP-sensitive potassium channels activity, increased cytosolic antioxidant capacity, and altered mitochondrial proteins production and phenotype have been hypothesized among the cellular mechanisms responsible for ex- ercise-induced cardioprotection [23]. However, the exact mechanism of this training-induced beneficial effect still remains a matter of debate. Mitochondria are dynamic organelles, the life cycle of which in- cludes their biogenesis (formation of new mitochondria), maintenance (preservation of a normal, healthy, metabolically active population of https://doi.org/10.1016/j.lfs.2018.10.035 Received 19 September 2018; Received in revised form 16 October 2018; Accepted 18 October 2018 ⁎ Corresponding author at: Department of Exercise Physiology, Faculty of Sport Sciences, University of Guilan, Khalij Fars Highway (5th Kilo Meter of Ghazvin Road), Rasht 4199613776, Iran. E-mail address: damirchi@guilan.ac.ir (A. Damirchi). Life Sciences 213 (2018) 102–108 Available online 22 October 2018 0024-3205/ © 2018 Elsevier Inc. All rights reserved. T