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Myofilament Remodeling and Function Is More Impaired in Peripartum Cardiomyopathy Compared with Dilated Cardiomyopathy and Ischemic Heart Disease.

Authors
  • Bollen, Ilse A E1
  • Ehler, Elisabeth2
  • Fleischanderl, Karin2
  • Bouwman, Floor3
  • Kempers, Lanette3
  • Ricke-Hoch, Melanie4
  • Hilfiker-Kleiner, Denise4
  • Dos Remedios, Cristobal G5
  • Krüger, Martina6
  • Vink, Aryan7
  • Asselbergs, Folkert W8
  • van Spaendonck-Zwarts, Karin Y9
  • Pinto, Yigal M10
  • Kuster, Diederik W D11
  • van der Velden, Jolanda12
  • 1 Department of Physiology, VU University Medical Center, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands. Electronic address: [email protected] , (Netherlands)
  • 2 Randall Division of Cell and Molecular Biophysics and Cardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College London, London, United Kingdom. , (United Kingdom)
  • 3 Department of Physiology, VU University Medical Center, Amsterdam, the Netherlands. , (Netherlands)
  • 4 Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany. , (Germany)
  • 5 Bosch Institute, Discipline of Anatomy and Histology, University of Sydney, Sydney, New South Wales, Australia. , (Australia)
  • 6 Institute of Cardiovascular Physiology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. , (Germany)
  • 7 Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands. , (Netherlands)
  • 8 Division Heart and Lungs, Department of Cardiology, University of Utrecht, University Medical Center Utrecht, Utrecht, the Netherlands; Durrer Center for Cardiogenetic Research, Netherlands Heart Institute, Utrecht, the Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom. , (United Kingdom)
  • 9 Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands; Department of Clinical Genetics, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, the Netherlands. , (Netherlands)
  • 10 Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands; Amsterdam Medical Center Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, the Netherlands. , (Netherlands)
  • 11 Department of Physiology, VU University Medical Center, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands. , (Netherlands)
  • 12 Department of Physiology, VU University Medical Center, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands; Netherlands Heart Institute, Utrecht, the Netherlands. , (Netherlands)
Type
Published Article
Journal
American Journal Of Pathology
Publisher
Elsevier
Publication Date
Dec 01, 2017
Volume
187
Issue
12
Pages
2645–2658
Identifiers
DOI: 10.1016/j.ajpath.2017.08.022
PMID: 28935576
Source
Medline
License
Unknown

Abstract

Peripartum cardiomyopathy (PPCM) and dilated cardiomyopathy (DCM) show similarities in clinical presentation. However, although DCM patients do not recover and slowly deteriorate further, PPCM patients show either a fast cardiac deterioration or complete recovery. The aim of this study was to assess if underlying cellular changes can explain the clinical similarities and differences in the two diseases. We, therefore, assessed sarcomeric protein expression, modification, titin isoform shift, and contractile behavior of cardiomyocytes in heart tissue of PPCM and DCM patients and compared these with nonfailing controls. Heart samples from ischemic heart disease (ISHD) patients served as heart failure control samples. Passive force was only increased in PPCM samples compared with controls, whereas PPCM, DCM, and ISHD samples all showed increased myofilament Ca2+ sensitivity. Length-dependent activation was significantly impaired in PPCM compared with controls, no impairment was observed in ISHD samples, and DCM samples showed an intermediate response. Contractile impairments were caused by impaired protein kinase A (PKA)-mediated phosphorylation because exogenous PKA restored all parameters to control levels. Although DCM samples showed reexpression of EH-myomesin, an isoform usually only expressed in the heart before birth, PPCM and ISHD did not. The lack of EH-myomesin, combined with low PKA-mediated phosphorylation of myofilament proteins and increased compliant titin isoform, may explain the increase in passive force and blunted length-dependent activation of myofilaments in PPCM samples.

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