Cardiomyocyte Hypocontractility and Reduced Myofibril Density in End-Stage Pediatric Cardiomyopathy

Bollen, Ilse A. E.; Meulen, Marijke van der; Goede, Kyra de; Kuster, Diederik W.D.; Dalinghaus, Michiel; Velden, Jolanda van der

doi:10.3389/fphys.2017.01103

Cited by 18 publications

(16 citation statements)

References 41 publications

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“…[17] Isometric force measurements Force measurements were performed in mechanically isolated single, membrane-permeabilized, cardiomyocytes as described previously. [18,19] In short, we measured passive tension at a range of sarcomere lengths (SL)(1.8-2.4 μm). All passive forces were normalized to cardiomyocyte cross-sectional area (CSA) (i.e.…”

Section: Echocardiographic Measurementsmentioning

confidence: 99%

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Sex-specific cardiac remodeling in early and advanced stages of hypertrophic cardiomyopathy

et al. 2020

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Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiac disease with a prevalence of 1:500 to 1:200. While most patients show obstructive HCM and a relatively stable clinical phenotype (stage II), a small group of patients progresses to end-stage HCM (stage IV) within a relatively brief period. Previous research has shown sex-differences in stage II HCM with more diastolic dysfunction in female than in male patients. Moreover, female patients more often show progression to heart failure. Here we investigated if differences in functional and structural properties of the heart may underlie sex-differences in disease progression from stage II to stage IV HCM. Cardiac tissue from stage II and IV patients was obtained during myectomy (n = 54) and heart transplantation (n = 10), respectively. Isometric force was measured in membrane-permeabilized cardiomyocytes to define active and passive myofilament force development. Titin isoform composition was assessed using gel electrophoresis, and the amount of fibrosis and capillary density were determined with histology. In accordance with disease stage-dependent adverse cardiac remodeling end-stage patients showed a thinner interventricular septal wall and larger left ventricular and atrial diameters compared to stage II patients. Cardiomyocyte contractile properties and fibrosis were comparable between stage II and IV, while capillary density was significantly lower in stage IV compared to stage II. Women showed more adverse cellular remodeling compared to men at stage II, evident from more compliant titin, more fibrosis and lower capillary density. However, the disease stage-dependent reduction in capillary density was largest in men. In conclusion, the more severe cellular remodeling in female compared to male stage II patients suggests a more advanced disease stage at the time of myectomy in women. Changes in cardiomyocyte contractile properties do not explain the progression of stage II to stage IV, while reduced capillary density may underlie disease progression to end-stage heart failure.

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Section: Echocardiographic Measurementsmentioning

confidence: 99%

“…Titin isoform gel electrophoresis was performed as previously described. [19,20] Samples were measured in triplicate, of which the mean was used. A. Mutations present in the patient samples.…”

Section: Protein Analysesmentioning

confidence: 99%

Sex-specific cardiac remodeling in early and advanced stages of hypertrophic cardiomyopathy

et al. 2020

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“…The end-diastolic volume increase causes a decrease in left ventricular ejection fraction [91]. A decrease in myofibril density was also observed in the case of end-stage pediatric cardiomyopathy [58] and congenital dilated cardiomyopathy with mutation in the structural protein filamin-C [92]. …”

Section: Contractile Properties Of Hcm and Dcm Heartsmentioning

confidence: 99%

Cardiomyopathies and Related Changes in Contractility of Human Heart Muscle

Vikhorev

Vikhoreva

2018

IJMS

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About half of hypertrophic and dilated cardiomyopathies cases have been recognized as genetic diseases with mutations in sarcomeric proteins. The sarcomeric proteins are involved in cardiomyocyte contractility and its regulation, and play a structural role. Mutations in non-sarcomeric proteins may induce changes in cell signaling pathways that modify contractile response of heart muscle. These facts strongly suggest that contractile dysfunction plays a central role in initiation and progression of cardiomyopathies. In fact, abnormalities in contractile mechanics of myofibrils have been discovered. However, it has not been revealed how these mutations increase risk for cardiomyopathy and cause the disease. Much research has been done and still much is being done to understand how the mechanism works. Here, we review the facts of cardiac myofilament contractility in patients with cardiomyopathy and heart failure.

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“…Patel et al also associated adult hypertrophied cardiomyocytes with increased sarcomere thickness; however, cardiomyocytes from pediatric HF patients did not demonstrate these changes in sarcomeric thickness. Interestingly, density of myofibrils have been reported to increase in pediatric patients [51], contributing to the overall conclusion that the response of the pediatric myocardium to an unknown pathologic insult is not the same as adults.…”

Section: Cardiac Remodeling Across the Life-coursementioning

confidence: 99%

From pediatrics to geriatrics: Mechanisms of heart failure across the life-course

Woulfe

Bruns

2019

Journal of Molecular and Cellular Cardiology

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Heart failure (HF) is a significant public health problem and a disease with high 5-year mortality. Although age is the primary risk factor for development of HF, it is a disease which impacts patients of all ages. Historically, HF has been studied as a one-size fits all strategy- with the majority of both clinical and basic science investigations employing adult male subjects or adult male pre-clinical animal models. We postulate that inclusion of biological variables in HF studies is necessary to improve our understanding of mechanisms of HF and improve outcomes. In this review, we will discuss age-specific differences in HF patients, particularly focusing on the pediatric and geriatric age groups. In addition, we will also discuss the biological variable of sex. Characterizing and understanding the mechanistic differences in these distinct HF populations can provide insights that will benefit and personalize therapeutic interventions. Further, we propose that future investigations into the cellular mechanisms involved in the developing and juvenile heart may provide valuable insights for targets that would be beneficial in aging patients.

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Cardiomyocyte Hypocontractility and Reduced Myofibril Density in End-Stage Pediatric Cardiomyopathy

Cited by 18 publications

References 41 publications

Sex-specific cardiac remodeling in early and advanced stages of hypertrophic cardiomyopathy

Sex-specific cardiac remodeling in early and advanced stages of hypertrophic cardiomyopathy

Cardiomyopathies and Related Changes in Contractility of Human Heart Muscle

From pediatrics to geriatrics: Mechanisms of heart failure across the life-course

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