Contribution of Acquired Factors to the Pathogenesis of Dilated Cardiomyopathy - The Cause of Dilated Cardiomyopathy: Genetic or Acquired? (Acquired-Side) -

Yoshikawa, Tsutomu

doi:10.1253/circj.cj-11-0373

Cited by 18 publications

(4 citation statements)

References 56 publications

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“…Around 35% of DCM cases are familial inherited, while the other 65% are acquired throughout the patient ’ s life. Acquired DCM can arise from environmental infections, autoimmune diseases, endocrine diseases, muscular dystrophy, and/or long-term alcohol abuse [ 39 , 40 ]. DCM symptoms vary and can present as fatigue, weight gain, thromboembolism, and chest pain [ 41 , 42 ].…”

Section: The Cardiomyopathiesmentioning

confidence: 99%

Arrhythmogenic Cardiomyopathy: Exercise Pitfalls, Role of Connexin-43, and Moving beyond Antiarrhythmics

Coscarella

Landim-Vieira

Pinto

et al. 2022

IJMS

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Arrhythmogenic Cardiomyopathy (ACM), a Mendelian disorder that can affect both left and right ventricles, is most often associated with pathogenic desmosomal variants that can lead to fibrofatty replacement of the myocardium, a pathological hallmark of this disease. Current therapies are aimed to prevent the worsening of disease phenotypes and sudden cardiac death (SCD). Despite the use of implantable cardioverter defibrillators (ICDs) there is no present therapy that would mitigate the loss in electrical signal and propagation by these fibrofatty barriers. Recent studies have shown the influence of forced vs. voluntary exercise in a variety of healthy and diseased mice; more specifically, that exercised mice show increased Connexin-43 (Cx43) expression levels. Fascinatingly, increased Cx43 expression ameliorated the abnormal electrical signal conduction in the myocardium of diseased mice. These findings point to a major translational pitfall in current therapeutics for ACM patients, who are advised to completely cease exercising and already demonstrate reduced Cx43 levels at the myocyte intercalated disc. Considering cardiac dysfunction in ACM arises from the loss of cardiomyocytes and electrical signal conduction abnormalities, an increase in Cx43 expression—promoted by low to moderate intensity exercise and/or gene therapy—could very well improve cardiac function in ACM patients.

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Section: The Cardiomyopathiesmentioning

confidence: 99%

Arrhythmogenic Cardiomyopathy: Exercise Pitfalls, Role of Connexin-43, and Moving beyond Antiarrhythmics

Coscarella

Landim-Vieira

Pinto

et al. 2022

IJMS

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“…In this disorder, dilation and impaired contraction of the left or both ventricles develops [1]. DCM is characterized by dilated ventricles and systolic dysfunction, and the clinical symptom of non-ischemic DCM is heart failure, which is often associated with arrhythmia and sudden death [2,3]. Correct evaluation of the patient's myocardial function has important clinical significance in the diagnosis, therapeutic effect assessment and prognosis in non-ischemic DCM patients.…”

Section: Introductionmentioning

confidence: 99%

Preliminary clinical study of left ventricular myocardial strain in patients with non-ischemic dilated cardiomyopathy by three-dimensional speckle tracking imaging

Duan

Xie

Wang

et al. 2012

Cardiovasc Ultrasound

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BackgroundNon-ischemic dilated cardiomyopathy (DCM) is the most common cardiomyopathy worldwide, with significant mortality. Correct evaluation of the patient's myocardial function has important clinical significance in the diagnosis, therapeutic effect assessment and prognosis in non-ischemic DCM patients. This study evaluated the feasibility of three-dimensional speckle tracking imaging (3D-STE) for assessment of the left ventricular myocardial strain in patients with non-ischemic dilated cardiomyopathy (DCM).MethodsApical full-volume images were acquired from 65 patients with non-ischemic DCM (DCM group) and 59 age-matched normal controls (NC group), respectively. The following parameters were measured by 3D-STE: the peak systolic radial strain (RS), circumferential strain (CS), longitudinal strain (LS) of each segment. Then all the parameters were compared between the two groups.ResultsThe peak systolic strain in different planes had certain regularities in normal groups, radial strain (RS) was the largest in the mid region, the smallest in the apical region, while circumferential strain (CS) and longitudinal strain (LS) increased from the basal to the apical region. In contrast, the regularity could not be applied to the DCM group. RS, CS, LS were significantly decreased in DCM group as compared with NC group (P < 0.001 for all). The interobserver, intraobserver and test-retest reliability were acceptable.Conclusions3D-STE is a reliable tool for evaluation of left ventricular myocardial strain in patients with non-ischemic DCM, with huge advantage in clinical application.

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“…1 Heart failure is known to be related to various aetiological genetic abnormalities, mitochondrial dysfunction, excessive alcohol consumption, metabolic disorders, viral infections, and oxidative stress. 2,3 Most of the genetic causes are mutations in sarcomeric specific genes and sarcomeric elements play key roles in the generation and transmission of contractile force. 4,5 Moreover, DCM is known to cause arrhythmias, including atrioventricular (AV) block.…”

Section: Introductionmentioning

confidence: 99%

Dilated cardiomyopathy-linked heat shock protein family D member 1 mutations cause up-regulation of reactive oxygen species and autophagy through mitochondrial dysfunction

Enomoto

Mittal

Inomata

et al. 2020

Cardiovascular Research

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Background During heart failure, the levels of circulatory HSPD1 (HSP60) increase. However, its underlying mechanism is still unknown. The apical domain of HSPD1 is conserved throughout evolution. We found a point mutation in HSPD1 in a familial dilated cardiomyopathy (DCM) patient. A similar point mutation in HSPD1 in the zebrafish mutant, nbl, led to loss of its regenerative capacity and development of pericardial edema under heat stress condition. In this study, we aimed to determine the direct involvement of HSPD1 in the development of DCM. Methods and Results By Sanger method, we found a point mutation (Thr320Ala) in the apical domain of HSPD1, in one familial DCM patient, which was four amino acids away from the point mutation (Val324Glu) in the nbl mutant zebrafish. The nbl mutants showed atrioventricular block and sudden death at eight months post-fertilization. Histological and microscopic analysis of the nbl mutant hearts showed decreased ventricular wall thickness, elevated level of reactive oxygen species (ROS), increased fibrosis, mitochondrial damage, and increased autophagosomes. mRNA and protein expression of autophagy-related genes significantly increased in nbl mutants. We established HEK293 stable cell lines of WT, nbl-type, and DCM-type HSPD1, with tetracycline-dependent expression. Compared to WT, both nbl- and DCM-type cells showed decreased cell growth, increased expression of ROS and autophagy-related genes, inhibition of the activity of mitochondrial electron transport chain complexes III and IV, and decreased mitochondrial fission and fusion. Conclusions Mutations in HSPD1 caused mitochondrial dysfunction and induced mitophagy. Mitochondrial dysfunction caused increased ROS and cardiac atrophy. Translational Perspective The aged heart is more susceptible to stress despite the increased compensatory chaperones/co-chaperones activity. Here, we identified a point mutation in HSPD1 in a human DCM family. Using zebrafish, we demonstrated that functional inactivation of HSPD1 resulted in increased ROS level and mitophagy, thereby resulting in heart failure at a relatively early age. Inhibition of ROS activity by antioxidants decreased cell death and mitophagy. This work identifies the key role of HSPD1 in cardiac muscle protection and suggests the supplementation of antioxidants may improve the cardiac function through the mitochondrial ROS pathway in patients with chronic heart failure.

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Contribution of Acquired Factors to the Pathogenesis of Dilated Cardiomyopathy - The Cause of Dilated Cardiomyopathy: Genetic or Acquired? (Acquired-Side) -

Cited by 18 publications

References 56 publications

Arrhythmogenic Cardiomyopathy: Exercise Pitfalls, Role of Connexin-43, and Moving beyond Antiarrhythmics

Arrhythmogenic Cardiomyopathy: Exercise Pitfalls, Role of Connexin-43, and Moving beyond Antiarrhythmics

Preliminary clinical study of left ventricular myocardial strain in patients with non-ischemic dilated cardiomyopathy by three-dimensional speckle tracking imaging

Dilated cardiomyopathy-linked heat shock protein family D member 1 mutations cause up-regulation of reactive oxygen species and autophagy through mitochondrial dysfunction

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