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Adaptations of cytoarchitecture in human dilated cardiomyopathy

Marlene Pluess1, Gregor Daeubler1, Cristobal G Dos Remedios2

  • 1Randall Division of Cell and Molecular Biophysics and Cardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.

Biophysical Reviews
|May 17, 2017
PubMed

Insights

Dilated cardiomyopathy (DCM) involves altered heart cell structures, including the intercalated disc and sarcomere M-band. These cytoarchitectural changes in cardiomyocytes likely contribute to reduced heart function in DCM patients.

Area of Science:

  • Cardiovascular Biology
  • Cellular Cardiology
  • Cardiac Pathology

Background:

  • Dilated cardiomyopathy (DCM) presents with fibrosis and necrosis, unlike the myocyte disarray typical of hypertrophic cardiomyopathy.
  • Previous research explored subcellular cytoarchitectural alterations in mouse models of DCM.

Purpose of the Study:

  • To investigate subcellular alterations in the cytoarchitecture of heart cells in dilated cardiomyopathy (DCM).
  • To analyze changes in the intercalated disc and sarcomere M-band composition.
  • To examine cardiomyocyte size control in human DCM samples.

Main Methods:

  • Analysis of subcellular structures in mouse models of DCM.
  • Investigation of intercalated disc organization and composition.
  • Examination of sarcomere M-band composition, focusing on myomesin isoforms.
  • Analysis of human heart tissue samples from the Sydney Human Heart Tissue Bank.

Main Results:

  • Significant alterations were found in the organization and composition of the intercalated disc in DCM.
  • A shift in M-band composition towards the embryonic heart (EH)-myomesin isoform was observed.
  • Human DCM samples showed similar structural findings to mouse models.
  • Evidence of dramatic changes in cardiomyocyte size control was found in human DCM samples.

Conclusions:

  • Alterations in intercalated disc and M-band composition are key features of DCM cytoarchitecture.
  • Changes in cardiomyocyte size control contribute to DCM pathology.
  • These cytoarchitectural modifications likely underlie the decreased functional output observed in DCM.

Keywords:
CytoskeletonDilated cardiomyopathyForminIntercalated discM-band

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