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

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.

Self-Paced Free-Running Wheel Mimics High-Intensity Interval Training Impact on Rats’ Functional, Physiological, Biochemical, and Morphological Features

“…In addition, it is also frequently used to avoid further impairments caused by lack of metabolic and mechanical stimuli or as a specific exercise regimen established to induce organic adaptations and thus, to positively modulate tissue phenotype (Kariya et al, 2004; Marques-Aleixo et al, 2016; Rocha-Rodrigues et al, 2016, 2017). In accordance with data from previous studies (Deloux et al, 2017; Stolle et al, 2017; Zhou et al, 2017), our results suggest that FRW induced significant adaptations regarding animals’ physical fitness. In fact, as previously mentioned, the adaptations produced by both exercise models were significantly different compared to the SED group along the different analyzed parameters.…”

Aged Nicotinamide Riboside Kinase 2 Deficient Mice Present an Altered Response to Endurance Exercise Training

“…We have shown recently that Nmrk2 levels are strongly induced in the context dilated cardiomyopathy triggered by heart-specific deletion of the SRF transcription factor and that NR-supplemented diet or voluntary wheel running delays the onset of heart failure in this model (Deloux et al, 2017 ; Diguet et al, 2018 ). NMRK2, a striated muscle specific kinase has recently been shown to be required in muscle cells, in redundancy with the more ubiquitous NMRK1, to respond to the boosting effect of NR on NAD level (Fletcher et al, 2017 ).…”

The role of CD36 in cardiovascular disease

“… 145 The decrease in CD36 in pathological cardiac hypertrophy and the up-regulation in physiological cardiac hypertrophy may be related to PPARα and peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α). Physical exercise increases the expression of PPARα 146 , 147 and PGC1α 148 , 149 in the heart, while cardiac pressure overload reduces them 150 , 151 ( Figure 4 ). The promoter region of CD36 contains PPARα response elements.…”