Blunted cardiac beta-adrenergic response as an early indication of cardiac dysfunction in Duchenne muscular dystrophy

Li, Ying; Zhang, Shuai; Zhang, Xiaoying; Li, Jing; Ai, Xinghao; Zhang, Li; Yu, Daohai; Ge, Shuping; Peng, Yizhi; Chen, Xiongwen

doi:10.1093/cvr/cvu119

Cited by 35 publications

(53 citation statements)

References 31 publications

(49 reference statements)

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“…Consequently, it does not surprise that dysferlindeficiency is linked to cardiomyopathy development in mice [4,7,9] and in LGMD2B patients [7,8]. Whereas dilated cardiomyopathy in the context of dystrophin-deficiency was associated with substantial cardiac voltage-dependent ion channel abnormalities [10][11][12][13], here we report basically normal ion channel properties in dysferlin-deficient (dysf) cardiomyocytes. Together with normal ECGs in dysf mice these results suggest that dysferlindeficiency does not impair cardiac electrophysiology.…”

Section: Discussionmentioning

confidence: 46%

“…We and others have recently reported that dystrophin-deficient cardiomyocytes derived from adult mdx and mdx-utr mice (mouse models of Duchenne muscular dystrophy) have significantly enhanced L-type calcium currents [12,13]. Moreover, calcium channel inactivation was impaired in dystrophic myocytes [12,14,15].…”

Section: Calcium Channels In Wt and Dysf Cardiomyocytesmentioning

confidence: 96%

“…We and others have recently reported that dystrophin-deficient ventricular cardiomyocytes isolated from the hearts of mouse models of Duchenne muscular dystrophy (mdx, only dystrophin-deficient; mdx-utr, dystrophin-and utrophin-deficient) [10][11][12][13] show significant abnormalities in voltage-dependent ion channel expression and function. These abnormal "dystrophic" cardiac ion channel properties, i.e.…”

Section: Introductionmentioning

confidence: 98%

“…These abnormal "dystrophic" cardiac ion channel properties, i.e. enhanced L-type Ca v 1.2 calcium currents [12,13], slowed Ca v 1.2 channel inactivation [12,14,15], and reduced Na v 1.5 sodium currents [10,11], may contribute to the pathophysiology in dystrophic cardiomyopathy. Direct regulation of Ca v 1.2 channels by dystrophin accords with the finding that, in mouse cardiomyocytes, Ca v 1.2 colocalizes with dystrophin [14].…”

Section: Introductionmentioning

confidence: 99%

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Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes

Rubi

Gawali

Kubista

et al. 2015

Cell Physiol Biochem

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Background/Aims: Dysferlin plays a decisive role in calcium-dependent membrane repair in myocytes. Mutations in the encoding DYSF gene cause a number of myopathies, e.g. limb-girdle muscular dystrophy type 2B (LGMD2B). Besides skeletal muscle degenerative processes, dysferlin deficiency is also associated with cardiac complications. Thus, both LGMD2B patients and dysferlin-deficient mice develop a dilated cardiomyopathy. We and others have recently reported that dystrophin-deficient ventricular cardiomyocytes from mouse models of Duchenne muscular dystrophy show significant abnormalities in voltage-dependent ion channels, which may contribute to the pathophysiology in dystrophic cardiomyopathy. The aim of the present study was to investigate if dysferlin, like dystrophin, is a regulator of cardiac ion channels. Methods and Results: By using the whole cell patch-clamp technique, we compared the properties of voltage-dependent calcium and sodium channels, as well as action potentials in ventricular cardiomyocytes isolated from the hearts of normal and dysferlin-deficient (dysf) mice. In contrast to dystrophin deficiency, the lack of dysferlin did not impair the ion channel properties and left action potential parameters unaltered. In connection with normal ECGs in dysf mice these results suggest that dysferlin deficiency does not perturb cardiac electrophysiology. Conclusion: Our study demonstrates that dysferlin does not regulate cardiac voltage-dependent ion channels, and implies that abnormalities in cardiac ion channels are not a universal characteristic of all muscular dystrophy types.

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Section: Discussionmentioning

confidence: 46%

Section: Calcium Channels In Wt and Dysf Cardiomyocytesmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes

Rubi

Gawali

Kubista

et al. 2015

Cell Physiol Biochem

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“…The image was acquired with an Odyssey infrared imaging system (Li-Cor Bioscience, Lincoln, NE, USA). All immunoblotting experiments were repeated at least three times3637.…”

Section: Methodsmentioning

confidence: 99%

Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling

Shao

Peng

et al. 2016

Sci Rep

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Previously we showed that Ani (anisodamine)/Neo (neostigmine) combination produced anti-shock effect via activating α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we aim to investigate the therapeutic effect and underlying mechanisms of Ani/Neo combination in acute lethal crush syndrome (CS). In rat and rabbit CS models, Ani/Neo combination increased the 24 h survival rates, improved hemodynamics and decreased the levels of creatine kinase, MB isoenzyme of creatine kinase, blood urea nitrogen, creatinine, K+ in serum. It also decreased the levels of H2O2, myeloperoxidase (MPO) and nitric oxide (NO) in serum and compressed muscle in rat CS model. In wild-type (WT) mice with CS, Ani/Neo combination increased 24 h survival rate and decreased the levels of H2O2, MPO, NO, TNFα, IL-6 and IL-10 in compressed muscle. These effects were attenuated by α7nAChR knockout (KO). Moreover, Ani/Neo combination prevented the decrease of phosphorylation of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) induced by CS. These effects of Ani/Neo in CS mice were cancelled by methyllycaconitine (α7nAChR antagonist) and α7nAChR KO. Collectively, our results demonstrate that Ani/Neo combination could produce therapeutic effects in CS. The underlying mechanism involves the activation of α7nAChR-dependent JAK2-STAT3 signaling pathway.

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Cyclo His‐Pro Attenuates Muscle Degeneration in Murine Myopathy Models

De Masi,

Zanou,

Strotjohann

et al. 2024

Advanced Science

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Among the inherited myopathies, a group of muscular disorders characterized by structural and metabolic impairments in skeletal muscle, Duchenne muscular dystrophy (DMD) stands out for its devastating progression. DMD pathogenesis is driven by the progressive degeneration of muscle fibers, resulting in inflammation and fibrosis that ultimately affect the overall muscle biomechanics. At the opposite end of the spectrum of muscle diseases, age‐related sarcopenia is a common condition that affects an increasing proportion of the elderly. Although characterized by different pathological mechanisms, DMD and sarcopenia share the development of progressive muscle weakness and tissue inflammation. Here, the therapeutic effects of Cyclo Histidine‐Proline (CHP) against DMD and sarcopenia are evaluated. In the mdx mouse model of DMD, it is shown that CHP restored muscle contractility and force production, accompanied by the reduction of fibrosis and inflammation in skeletal muscle. CHP furthermore prevented the development of cardiomyopathy and fibrosis in the diaphragm, the two leading causes of death for DMD patients. CHP also attenuated muscle atrophy and functional deterioration in a mouse model of age‐related sarcopenia. These findings from two different models of muscle dysfunction hence warrant further investigation into the effects of CHP on muscle pathologies in animal models and eventually in patients.

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Blunted cardiac beta-adrenergic response as an early indication of cardiac dysfunction in Duchenne muscular dystrophy

Abstract: In young mdx mice, the myocyte increases its contractile function to compensate for myocyte loss. However, these myocytes with enhanced baseline function have reduced potential for stimulation, decreased β1-AR density/sensitivity, leading to blunted cardiac beta-adrenergic response.

Cited by 35 publications

References 31 publications

Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes

Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes

Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling

Cyclo His‐Pro Attenuates Muscle Degeneration in Murine Myopathy Models

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