Depressed myocardial fatty acid metabolism in patients with muscular dystrophy

Momose, Mitsuru; Iguchi, Nobuo; Imamura, Kimiharu; Usui, Hidemi; Ueda, Toshihisa; Miyamoto, Kenjiro; Inaba, Shinji

doi:10.1016/s0960-8966(01)00191-2

Cited by 18 publications

(14 citation statements)

References 28 publications

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“…The metabolic shift from LCFA to CHO that we observed in young mdx mice concurs with findings from cardiac positron emission tomography studies performed in patients with DMD using 18 F-deoxyglucose or a radioiodinated branched fatty acid ( [57][58][59][60]. Although metabolic flux parameters relative to LCFA partitioning between oxidation and triglyceride synthesis were not specifically assessed in our study, our results indicated that the contribution of endogenous substrates (postulated to be triglycerides) to acetyl-CoA production was similar to controls at this early stage of the cardiomyopathic process, presumably because lower LCFA oxidation was compensated by increased CHO oxidation.…”

Section: Alterations In Mitochondrial Substrate Metabolism In the Earsupporting

confidence: 89%

Alterations in mitochondrial function as a harbinger of cardiomyopathy: Lessons from the dystrophic heart

Burelle

Khairallah

Ascah

et al. 2010

Journal of Molecular and Cellular Cardiology

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While compelling evidence supports the central role of mitochondrial dysfunction in the pathogenesis of heart failure, there is comparatively less information available on mitochondrial alterations that occur prior to failure. Building on our recent work with the dystrophin-deficient mdx mouse heart, this review focuses on how early changes in mitochondrial functional phenotype occur prior to overt cardiomyopathy and may be a determinant for the development of adverse cardiac remodelling leading to failure. These include alterations in energy substrate utilization and signalling of cell death through increased permeability of mitochondrial membranes, which may result from abnormal calcium handling, and production of reactive oxygen species. Furthermore, we will discuss evidence supporting the notion that these alterations in the dystrophin-deficient heart may represent an early "subclinical" signature of a defective nitric oxide/cGMP signalling pathway, as well as the potential benefit of mitochondria-targeted therapies. While the mdx mouse is an animal model of Duchenne muscular dystrophy (DMD), changes in the structural integrity of dystrophin, the mutated cytoskeletal protein responsible for DMD, have also recently been implicated as a common mechanism for contractile dysfunction in heart failure. In fact, altogether our findings support a critical role for dystrophin in maintaining optimal coupling between metabolism and contraction in the heart.

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Section: Alterations In Mitochondrial Substrate Metabolism In the Earsupporting

confidence: 89%

Alterations in mitochondrial function as a harbinger of cardiomyopathy: Lessons from the dystrophic heart

Burelle

Khairallah

Ascah

et al. 2010

Journal of Molecular and Cellular Cardiology

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“…Proton NMR analysis in biopsied skeletal muscle from DMD patients demonstrated, in addition to reduced levels of choline-containing lipids indicative of membrane abnormalities, a decrease in acetate-containing lipids that is indicative of reduced transport of fatty acids into mitochondria due to decreased carnitine concentrations (115 ). Indeed, in approximately 50% of DMD patients examined, a reduction in myocardial fatty acid metabolism was indicated by reduced uptake and metabolism of a radioiodinated branched fatty acid ( 118 ). As depicted in Fig.…”

mentioning

confidence: 88%

Delineating the role of alterations in lipid metabolism to the pathogenesis of inherited skeletal and cardiac muscle disorders

Saini-Chohan

Mitchell

Vaz

et al. 2012

Journal of Lipid Research

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“…Examinations are carried out at rest and after pharmacological or physical stress [15, 25, 26, 27]. Myocardial fatty acid metabolism can be assessed using the radio-iodinated branched fatty acid 15-( p -iodophenyl)-3(R,S)-methyl-penta-decanoic acid (BMIPP) [28]. The tracer iodine-123 meta-iodo-benzyl-guanidine is used to assess the myocardial sympathetic nervous system function [23].…”

Section: Examinations To Assess Cardiac Involvementmentioning

confidence: 99%

“…Applying 123 I-BMIPP scintigraphy, 8 of 9 DMD patients showed reduced BMIPP uptake. Only 1 of these patients had a normal ECG, and 7 patients had regional wall motion abnormalities [28]. …”

Section: Duchenne Muscular Dystrophymentioning

confidence: 99%

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The Heart in Human Dystrophinopathies

2003

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Dystrophinopathies are due to mutations in the dystrophin gene on chromosome Xp21.1 and comprise the allelic entities Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and X-linked dilative cardiomyopathy (XLDCM). In all three entities, the heart is affected to various degrees, depending on the stage of the disease and the type of the mutation (cardiac involvement, CI). The pathoanatomic evidence of CI in dystrophinopathies is the replacement of myocardium by connective tissue or fat. In DMD/BMD, the left ventricular posterobasal and lateral walls are most extensively affected, sparing the right ventricle and the atrium. Degree and dynamics of CI vary among the three entities. In DMD/BMD, CI usually remains subclinical in the early stages of the disease. Typical initial manifestations of CI in DMD/BMD are sinus tachycardia, tall R1 in V1, prominent Q in I, aVL, V6 or in II, III, and aVF, increased QT dispersion and possibly autonomic dysfunction. Initially, echocardiography is normal or shows regional wall motion abnormalities in areas of fibrosis. With spreading of fibrosis, left ventricular dysfunction and ventricular arrhythmias additionally occur. In the final stages of the disease, systolic function may lead to heart failure and sudden death. Subclinical or clinical CI is present in about 90% of the DMD/BMD patients but is the cause of death in only 20% of the DMD and 50% of the BMD patients. XLDCM is a rapidly progressive, almost exclusively myocardial disorder, starting in teenage males as heart failure due to dilative cardiomyopathy (CMP), leading to death from intractable heart failure within 1–2 years after diagnosis. Therapy of arrhythmias and CMP in all three disorders follows the established cardiological recommendations. Due to its protective effect, ACE inhibitors are recommended already at the early stages of the disease. β-Blockers may be an additional option if indicated.

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Depressed myocardial fatty acid metabolism in patients with muscular dystrophy

Cited by 18 publications

References 28 publications

Alterations in mitochondrial function as a harbinger of cardiomyopathy: Lessons from the dystrophic heart

Alterations in mitochondrial function as a harbinger of cardiomyopathy: Lessons from the dystrophic heart

Delineating the role of alterations in lipid metabolism to the pathogenesis of inherited skeletal and cardiac muscle disorders

The Heart in Human Dystrophinopathies

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