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

Ilse A.E. Bollen, Elisabeth Ehler, Karin Fleischanderl, Floor Bouwman, Lanette Kempers, Melanie Ricke-Hoch, Denise Hilfiker-Kleiner, Cristobal G. dos Remedios, Martina Krüger, Aryan Vink, Folkert W. Asselbergs, Karin Y. van Spaendonck-Zwarts, Yigal M. Pinto, Diederik W.D. Kuster, Jolanda van der Velden

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)2645-2658
Number of pages14
JournalAmerican Journal of Pathology
Volume187
Issue number12
DOIs
Publication statusPublished - 1 Dec 2017

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