Voluntary Exercise Improves Cardiac Function and Prevents Cardiac Remodeling in a Mouse Model of Dilated Cardiomyopathy

Robin Deloux; Damien Vitiello; Nathalie Mougenot; Philippe Noirez; Zhenlin Li; Mathias Mericskay; Arnaud Ferry; Onnik Agbulut

doi:10.3389/fphys.2017.00899

Voluntary Exercise Improves Cardiac Function and Prevents Cardiac Remodeling in a Mouse Model of Dilated Cardiomyopathy

Front Physiol. 2017 Nov 15:8:899. doi: 10.3389/fphys.2017.00899. eCollection 2017.

Authors

Robin Deloux^{1

2}, Damien Vitiello^{1

3

4}, Nathalie Mougenot⁵, Philippe Noirez^{3

4}, Zhenlin Li¹, Mathias Mericskay^{1

2}, Arnaud Ferry^{3

6}, Onnik Agbulut¹

Affiliations

¹ Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris-Seine, UMR Centre National de la Recherche Scientifique 8256, Biological Adaptation and Aging, Paris, France.
² UMR-S 1180, National Institute for Health and Medical Research, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
³ Sorbonne Paris Cité, Université Paris Descartes, Paris, France.
⁴ Institute for Research in Medicine and Epidemiology of Sport, EA7329, National Institute of Sport, Expertise and Performance, Université Paris Descartes, Paris, France.
⁵ Sorbonne Universités, UPMC University Paris 06, UMS28, Plateforme d'Expérimentation Coeur, Muscles, Vaisseaux, Paris, France.
⁶ Sorbonne Universités, UPMC University Paris 06, Institut de Myologie, UMR-S 794, National Institute for Health and Medical Research, UMR Centre National De La Recherche Scientifique 7215, Paris, France.

Abstract

Objective: Despite the indubitable beneficial effect of exercise to prevent of cardiovascular diseases, there is still a lack of studies investigating the impact of exercise in non-ischemic dilated cardiomyopathy. Here, we investigated the impact of voluntary exercise on cardiac function in a mouse model of non-ischemic dilated cardiomyopathy (αMHC-MerCreMer:Sf/Sf), induced by cardiac-specific inactivation of the Serum Response Factor. Materials and Methods: Seven days after tamoxifen injection, 20 αMHC-MerCreMer:Sf/Sf mice were assigned to sedentary (n = 8) and exercise (n = 12) groups. Seven additional αMHC-MerCreMer:Sf/Sf mice without tamoxifen injection were used as control. The exercise group performed 4 weeks of voluntary running on wheel (1.8 ± 0.12 km/day). Cardiac function, myocardial fibrosis, and mitochondrial energetic pathways were then blindly assessed. Results: Exercised mice exhibited a smaller decrease of left ventricular (LV) fractional shortening and ejection fraction compared to control mice. This was associated with a lower degree of LV remodeling in exercised mice, as shown by a lower LV end-systolic intrerventricular septal and posterior wall thickness decrease from baseline values compared to sedentary mice. Moreover, exercised mice displayed a reduced gene expression of atrial and brain natriuretic factors. These benefits were associated by a reduced level of myocardial fibrosis. In addition, exercised mice exhibited a higher mitochondrial aconitase, voltage-dependent anion-selective channel 1 and PPAR gamma coactivators-1 alpha proteins levels suggesting that the increase of mitochondrial biogenesis and/or metabolism slowed the progression of dilated cardiomyopathy in exercised animals. Conclusions: In conclusion, our results support the role of voluntary exercise to improve outcomes in non-ischemic dilated heart failure (HF) and also support its potential for a routine clinical use in the future.

Keywords: dilated cardiomyopathy; non-forced exercise; non-ischemic cardiac disease; wheel exercise.