Cardiac Involvement in Progressive Muscular Dystrophy of the Duchenne Type.

Ishikawa, Kinya

doi:10.1536/ihj.38.163

Cited by 29 publications

(14 citation statements)

References 88 publications

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“…This suggests acquired deterioration in b-adrenoreceptor responses. As the most frequent cardiac abnormality in DMD is sinus tachycardia occurring from childhood and persisting throughout life even in wheelchair-bound patients, 30 this finding in mdx mice presents somewhat of a contradiction, particularly as basal heart rates did not differ between strains in any age group. Autonomic defects have been reported in both the mdx model and patients with DMD.…”

Section: Discussionmentioning

confidence: 99%

Timeline of cardiac dystrophy in 3–18‐month‐old MDX mice

et al. 2010

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The dystrophin-deficient (mdx) mouse remains the most commonly used model for Duchenne muscular dystrophy (DMD). Mdx mice show a predominantly covert cardiomyopathy, the hallmark of which is fibrosis. We compared mdx and normal mice at six ages (3, 6, 9, 12, 15, and 18 months) using in vivo assessment of cardiac function, selective collagen staining, and measures of TGF-β mRNA, Evans blue dye infiltration, macrophage infiltration, and aortic wall thickness. Clear temporal progression was demonstrated, including early fragility of cardiomyocyte membranes, which has an unrelated impact on cardiac function but is associated with macrophage infiltration and fibrosis. Aortic wall thickness is less in older mdx mice. Mdx mice display impaired responses to inotropic challenge from a young age; this is indicative of altered adrenoreceptor function. We draw attention to the paradox of ongoing fibrosis in mdx hearts without a strong molecular signature (in the form of TGF-β mRNA expression).

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Section: Discussionmentioning

confidence: 99%

Timeline of cardiac dystrophy in 3–18‐month‐old MDX mice

et al. 2010

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“…5,25,34,35). Fibrotic lesions are thought to result from myocyte necrosis and subsequent inflammatory response.…”

Section: Grmdmentioning

confidence: 99%

Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs

Townsend¹,

Turner²,

Yasuda³

et al. 2010

J. Clin. Invest.

102

111

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Duchenne muscular dystrophy (DMD) is a fatal disease of striated muscle deterioration caused by lack of the cytoskeletal protein dystrophin. Dystrophin deficiency causes muscle membrane instability, skeletal muscle wasting, cardiomyopathy, and heart failure. Advances in palliative respiratory care have increased the incidence of heart disease in DMD patients, for which there is no cure or effective therapy. Here we have shown that chronic infusion of membrane-sealing poloxamer to severely affected dystrophic dogs reduced myocardial fibrosis, blocked increased serum cardiac troponin I (cTnI) and brain type natriuretic peptide (BNP), and fully prevented left-ventricular remodeling. Mechanistically, we observed a markedly greater primary defect of reduced cell compliance in dystrophic canine myocytes than in the mildly affected mdx mouse myocytes, and this was associated with a lack of utrophin upregulation in the dystrophic canine cardiac myocytes. Interestingly, after chronic poloxamer treatment, the poor compliance of isolated canine myocytes remained evident, but this could be restored to normal upon direct application of poloxamer. Collectively, these findings indicate that dystrophin and utrophin are critical to membrane stability-dependent cardiac myocyte mechanical compliance and that poloxamer confers a highly effective membrane-stabilizing chemical surrogate in dystrophin/utrophin deficiency. We propose that membrane sealant therapy is a potential treatment modality for DMD heart disease and possibly other disorders with membrane defect etiologies.

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“…14 The cardiac involvement in DMD is characterized pathologically by degeneration and fibrosis of the myocardium, centering around the posterolateral wall of the left ventricle. 15 Myocardial fibrosis was observed in most of the patients with DMD in an autopsy study. 16 Autopsy studies have shown that cardiomyopathy of Duchenne's muscular dystrophy (DMD) is characterized by fibrosis of the posterobasal and contiguous lateral wall of the left ventricle.…”

Section: Author's Replymentioning

confidence: 96%