Detection and management of cardiomyopathy in female dystrophinopathy carriers

Adachi, Kazutaka; Hashiguchi, Shuji; Saito, Miho; Kashiwagi, Setsuko; Miyazaki, Taeko; Kawai, Hisaomi; Yamada, Hirotsugu; Igarashi, Takashi; Akiyama, Masashi; Sugiyama, Takao; Kobayashi, Michio; Ishizaki, Masatoshi; Matsumura, T.; Mori‐Yoshimura, Madoka; Kimura, En

doi:10.1016/j.jns.2017.12.024

Cited by 23 publications

(19 citation statements)

References 29 publications

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“…With the prolongation of ethanol treatment time, the cardiomyocyte apoptosis increased. These results are consistent with previous studies (31–34).…”

Section: Discussionsupporting

confidence: 94%

MicroRNA‑186‑5p is expressed highly in ethanol‑induced cardiomyocytes and regulates apoptosis via the target gene XIAP

Liu

2019

Mol Med Report

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Ethanol has a toxic effect on the heart, resulting in cardiomyocyte damage. Long-term high intake of ethanol leads to a non-ischemic dilated cardiomyopathy termed alcoholic cardiomyopathy (ACM). However, the pathogenesis of alcoholic cardiomyopathy remains unclear. The apoptosis of cardiomyocytes serves an important role in the pathogenesis of ACM. X-linked inhibitor of apoptosis protein (XIAP) is an important anti-apoptotic protein in human tissue cells. To the best of our knowledge, no studies have reported on its function in ethanol-induced cardiomyopathy. Previous works have screened the ACM-associated differentially expressed microRNAs (miRs), including miR-186-5p and miR-488-3p. TargetScan bioinformatics software was used to predict 949 target genes associated with miR-186-5p, and XIAP was demonstrated to be a target of miR-186-5p. The present study firstly analyzed the levels of apoptosis in ethanol-treated cardiomyocytes using flow cytometry. Alterations in the expression levels of miR-186-5p and XIAP were subsequently evaluated in ethanol-treated AC16 cardiomyocytes to assess the specific molecular mechanisms of ethanol-induced cardiomyocyte apoptosis. The levels of apoptosis in AC16 cardiomyocytes increased following ethanol treatment, and further increased with the rise in concentration and action time of ethanol. The expression levels of miR-186-5p were upregulated, and the expression levels of XIAP were downregulated in ethanol-treated cardiomyocytes. miR-186-5p may regulate ethanol-induced apoptosis in cardiomyocytes using XIAP as the direct target gene. This study provides a novel therapeutic target for the prevention and treatment of ACM.

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“…With the prolongation of ethanol treatment time, the cardiomyocyte apoptosis increased. These results are consistent with previous studies (31–34).…”

Section: Discussionsupporting

confidence: 94%

MicroRNA‑186‑5p is expressed highly in ethanol‑induced cardiomyocytes and regulates apoptosis via the target gene XIAP

Liu

2019

Mol Med Report

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“…Numerous studies have failed to determine distinct genotype-phenotype correlations or an underlying mechanism to explain these heterogeneous cardiac phenotypes. Furthermore, the presence of cardiomyopathy in 10–60% of carrier females (CFs), females carrying dystrophin gene mutations, known as symptomatic CFs [ 8 ], lends further weight to the necessity for changes in research approach. A significant limiting factor in the development of therapeutic strategies for MD-CM is the lack of suitable human-tissue-based models capable of recapitulating disease phenotypes and providing insights on mechanisms linked to MD-CM onset and progression.…”

Section: Introductionmentioning

confidence: 99%

Dystrophin Cardiomyopathies: Clinical Management, Molecular Pathogenesis and Evolution towards Precision Medicine

D’Amario

Gowran

Canonico

et al. 2018

JCM

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Duchenne’s muscular dystrophy is an X-linked neuromuscular disease that manifests as muscle atrophy and cardiomyopathy in young boys. However, a considerable percentage of carrier females are often diagnosed with cardiomyopathy at an advanced stage. Existing therapy is not disease-specific and has limited effect, thus many patients and symptomatic carrier females prematurely die due to heart failure. Early detection is one of the major challenges that muscular dystrophy patients, carrier females, family members and, research and medical teams face in the complex course of dystrophic cardiomyopathy management. Despite the widespread adoption of advanced imaging modalities such as cardiac magnetic resonance, there is much scope for refining the diagnosis and treatment of dystrophic cardiomyopathy. This comprehensive review will focus on the pertinent clinical aspects of cardiac disease in muscular dystrophy while also providing a detailed consideration of the known and developing concepts in the pathophysiology of muscular dystrophy and forthcoming therapeutic options.

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“…However, in symptomatic female carriers, that information is poorly described in the literature, as well as the analysis of the performance in functional tasks. Rather, several studies characterize the cardiac symptomatology in female carriers of DMD 3,4,6 , and few report muscle disorders 7,8 .…”

mentioning

confidence: 99%

Functional performance and muscular strength in symptomatic female carriers of Duchenne muscular dystrophy

Silva

Anequini

Fávero

et al. 2020

Arq. Neuro-Psiquiatr.

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Duchenne muscular dystrophy (DMD) usually affects men. However, women are also affected in rare instances. Approximately 8% of female DMD carriers have muscle weakness and cardiomyopathy. The early identification of functional and motor impairments can support clinical decision making. Objective: To investigate the motor and functional impairments of 10 female patients with dystrophinopathy diagnosed with clinical, pathological, genetic and immunohistochemical studies. Methods: A descriptive study of a sample of symptomatic female carriers of DMD mutations. The studied variables were muscular strength and functional performance. Results: The prevalence was 10/118 (8.4%) symptomatic female carriers. Deletions were found in seven patients. The age of onset of symptoms in female carriers of DMD was quite variable. Pseudohypertrophy of calf muscles, muscular weakness, compensatory movements and longer timed performance on functional tasks were observed in most of the cases. Differently from males with DMD, seven female patients showed asymmetrical muscular weakness. The asymmetric presentation of muscle weakness was frequent and affected posture and functionality in some cases. The functional performance presents greater number of compensatory movements. Time of execution of activities was not a good biomarker of functionality for this population, because it does not change in the same proportion as the number of movement compensations. Conclusion: Clinical manifestation of asymmetrical muscle weakness and compensatory movements, or both can be found in female carriers of DMD mutations, which can adversely affect posture and functional performance of these patients.

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Detection and management of cardiomyopathy in female dystrophinopathy carriers

Cited by 23 publications

References 29 publications

MicroRNA‑186‑5p is expressed highly in ethanol‑induced cardiomyocytes and regulates apoptosis via the target gene XIAP

MicroRNA‑186‑5p is expressed highly in ethanol‑induced cardiomyocytes and regulates apoptosis via the target gene XIAP

Dystrophin Cardiomyopathies: Clinical Management, Molecular Pathogenesis and Evolution towards Precision Medicine

Functional performance and muscular strength in symptomatic female carriers of Duchenne muscular dystrophy

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