Early Myocardial Dysfunction and Benefits of Cardiac Treatment in Young X-Linked Duchenne Muscular Dystrophy Mice

Vincenti, Marie; Farah, Charlotte; Amédro, Pascal; Scheuermann, Valérie; Lacampagne, Alain; Cazorla, Olivier

doi:10.1007/s10557-021-07218-7

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…FKBP12 stabilizes the closed state of RyR [51] and reduces Ca 2+ leakage during the diastolic phase [52]. Early treatment with a RyR2 stabilizer prevents an excessive SR Ca 2+ leak and DMD-related cardiomyopathy in mice [53]. Here, we report that two months of anti-RANKL treatment also enhanced RyR and FKBP12 protein expression in the 13-month-old mdx mice.…”

Section: Discussionmentioning

confidence: 57%

RANKL Inhibition Reduces Cardiac Hypertrophy in mdx Mice and Possibly in Children with Duchenne Muscular Dystrophy

Marcadet

Juracic

Khan

et al. 2023

Cells

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Cardiomyopathy has become one of the leading causes of death in patients with Duchenne muscular dystrophy (DMD). We recently reported that the inhibition of the interaction between the receptor activator of nuclear factor κB ligand (RANKL) and receptor activator of nuclear factor κB (RANK) significantly improves muscle and bone functions in dystrophin-deficient mdx mice. RANKL and RANK are also expressed in cardiac muscle. Here, we investigate whether anti-RANKL treatment prevents cardiac hypertrophy and dysfunction in dystrophic mdx mice. Anti-RANKL treatment significantly reduced LV hypertrophy and heart mass, and maintained cardiac function in mdx mice. Anti-RANKL treatment also inhibited NFκB and PI3K, two mediators implicated in cardiac hypertrophy. Furthermore, anti-RANKL treatment increased SERCA activity and the expression of RyR, FKBP12, and SERCA2a, leading possibly to an improved Ca2+ homeostasis in dystrophic hearts. Interestingly, preliminary post hoc analyses suggest that denosumab, a human anti-RANKL, reduced left ventricular hypertrophy in two patients with DMD. Taken together, our results indicate that anti-RANKL treatment prevents the worsening of cardiac hypertrophy in mdx mice and could potentially maintain cardiac function in teenage or adult patients with DMD.

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Section: Discussionmentioning

confidence: 57%

RANKL Inhibition Reduces Cardiac Hypertrophy in mdx Mice and Possibly in Children with Duchenne Muscular Dystrophy

Marcadet

Juracic

Khan

et al. 2023

Cells

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“…Echocardiography is one of the commonly used imaging modalities for the assessment of left ventricular (LV) function. Speckle tracking echocardiography (STE) is a new technique that analyzes motion of acoustic reflections and STE parameters have been validated as treatment outcome biomarkers in the small animal models [15]. Early impaired cardiac function has been successfully detected in puppies, mice, and children using STE and LV strain assessments [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Two-dimensional speckle tracking echocardiography demonstrates improved myocardial function after intravenous infusion of bone marrow mesenchymal stem in the X-Linked muscular dystrophy mice

Liu

Yao

Pan

et al. 2022

BMC Cardiovasc Disord

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Background Bone marrow mesenchymal stem cells (BMSCs) are commonly used in regenerative medicine. However, it is not clear whether transplantation of BMSCs can improve cardiac function of the X-Linked Muscular Dystrophy Mice (mdx) and how to detect it. We aimed to investigate the role of speckle tracking echocardiography (STE) in detecting cardiac function of the BMSCs-transplanted mdx in comparison with the untreated mdx. Methods The experimental mice were divided into the BMSCs-transplanted mdx, untreated mdx, and control mice groups (n = 6 per group). The BMSCs were transplanted via tail vein injections into a subset of mdx at 20 weeks of age. After four weeks, the cardiac functional parameters of all the mice in the 3 groups were analyzed by echocardiography. Then, all the mice were sacrificed, and the cardiac tissues were harvested and analyzed by immunofluorescence. The serum biochemical parameters were also analyzed to determine the beneficial effects of BMSCs transplantation. Results Traditional echocardiography parameters did not show statistically significant differences after BMSCs transplantation for the three groups of mice. In comparison with the control group, mdx showed significantly lower left ventricular (LV) STE parameters in both the long-axis and short-axis LV images (P < 0.05). However, BMSCs-transplanted mdx showed improvements in several STE parameters including significant increases in a few STE parameters (P < 0.05). Immunofluorescence staining of the myocardium tissues showed statistically significant differences between the mdx and the control mice (P < 0.05), and the mdx transplanted with BMSCs demonstrated significantly improvement compared with the untreated mdx (P < 0.05). Conclusion This study demonstrated that the early reduction in the LV systolic and diastolic function in the mdx were accurately detected by STE. Furthermore, our study demonstrated that the transplantation of BMSCs significantly improved myocardial function in the mdx.

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Stabilizing Ryanodine Receptors Improves Left Ventricular Function in Juvenile Dogs With Duchenne Muscular Dystrophy

Cazorla

Barthélémy

et al. 2021

Journal of the American College of Cardiology

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Early Myocardial Dysfunction and Benefits of Cardiac Treatment in Young X-Linked Duchenne Muscular Dystrophy Mice

Cited by 3 publications

References 32 publications

RANKL Inhibition Reduces Cardiac Hypertrophy in mdx Mice and Possibly in Children with Duchenne Muscular Dystrophy

RANKL Inhibition Reduces Cardiac Hypertrophy in mdx Mice and Possibly in Children with Duchenne Muscular Dystrophy

Two-dimensional speckle tracking echocardiography demonstrates improved myocardial function after intravenous infusion of bone marrow mesenchymal stem in the X-Linked muscular dystrophy mice

Stabilizing Ryanodine Receptors Improves Left Ventricular Function in Juvenile Dogs With Duchenne Muscular Dystrophy

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