Myofilament dysfunction in cardiac disease from mice to men

Nazha Hamdani, Monique De Waard, Andrew E. Messer, Nicky M. Boontje, Viola Kooij, Sabine Van Dijk, Amanda Versteilen, Regis Lamberts, Daphne Merkus, Cris Dos Remedios, Dirk J. Duncker, A. Borbély, Z. Papp, Walter Paulus, Ger J M Stienen, Steven B. Marston, Jolanda Van Der Velden

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

In healthy human myocardium a tight balance exists between receptor-mediated kinases and phosphatases coordinating phosphorylation of regulatory proteins involved in cardiomyocyte contractility. During heart failure, when neurohumoral stimulation increases to compensate for reduced cardiac pump function, this balance is perturbed. The imbalance between kinases and phosphatases upon chronic neurohumoral stimulation is detrimental and initiates cardiac remodelling, and phosphorylation changes of regulatory proteins, which impair cardiomyocyte function. The main signalling pathway involved in enhanced cardiomyocyte contractility during increased cardiac load is the β-adrenergic signalling route, which becomes desensitized upon chronic stimulation. At the myofilament level, activation of protein kinase A (PKA), the down-stream kinase of the β-adrenergic receptors (β-AR), phosphorylates troponin I, myosin binding protein C and titin, which all exert differential effects on myofilament function. As a consequence of β-AR down-regulation and desensitization, phosphorylation of the PKA-target proteins within the cardiomyocyte may be decreased and alter myofilament function. Here we discuss involvement of altered PKA-mediated myofilament protein phosphorylation in different animal and human studies, and discuss the roles of troponin I, myosin binding protein C and titin in regulating myofilament dysfunction in cardiac disease. Data from the different animal and human studies emphasize the importance of careful biopsy procurement, and the need to investigate localization of kinases and phosphatases within the cardiomyocyte, in particular their co-localization with cardiac myofilaments upon receptor stimulation.

Original languageEnglish
Pages (from-to)189-201
Number of pages13
JournalJournal of Muscle Research and Cell Motility
Volume29
Issue number6-8
DOIs
Publication statusPublished - Dec 2008

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Phosphorylation
Myofibrils
Heart Diseases
Cardiac Myocytes
Phosphotransferases
Cyclic AMP-Dependent Protein Kinases
Phosphoric Monoester Hydrolases
Connectin
Troponin I
Animals
Proteins
Biopsy
Adrenergic Agents
Adrenergic Receptors
Chemical activation
Pumps
Myocardium
Down-Regulation
Heart Failure
myosin-binding protein C

Keywords

  • Heart failure
  • Kinase
  • Myofilament function
  • Phosphatase, adrenergic signalling
  • Phosphorylation
  • Protein kinase A

ASJC Scopus subject areas

  • Physiology
  • Cell Biology
  • Biochemistry

Cite this

Hamdani, N., De Waard, M., Messer, A. E., Boontje, N. M., Kooij, V., Van Dijk, S., ... Van Der Velden, J. (2008). Myofilament dysfunction in cardiac disease from mice to men. Journal of Muscle Research and Cell Motility, 29(6-8), 189-201. https://doi.org/10.1007/s10974-008-9160-y

Myofilament dysfunction in cardiac disease from mice to men. / Hamdani, Nazha; De Waard, Monique; Messer, Andrew E.; Boontje, Nicky M.; Kooij, Viola; Van Dijk, Sabine; Versteilen, Amanda; Lamberts, Regis; Merkus, Daphne; Dos Remedios, Cris; Duncker, Dirk J.; Borbély, A.; Papp, Z.; Paulus, Walter; Stienen, Ger J M; Marston, Steven B.; Van Der Velden, Jolanda.

In: Journal of Muscle Research and Cell Motility, Vol. 29, No. 6-8, 12.2008, p. 189-201.

Research output: Contribution to journalArticle

Hamdani, N, De Waard, M, Messer, AE, Boontje, NM, Kooij, V, Van Dijk, S, Versteilen, A, Lamberts, R, Merkus, D, Dos Remedios, C, Duncker, DJ, Borbély, A, Papp, Z, Paulus, W, Stienen, GJM, Marston, SB & Van Der Velden, J 2008, 'Myofilament dysfunction in cardiac disease from mice to men', Journal of Muscle Research and Cell Motility, vol. 29, no. 6-8, pp. 189-201. https://doi.org/10.1007/s10974-008-9160-y
Hamdani N, De Waard M, Messer AE, Boontje NM, Kooij V, Van Dijk S et al. Myofilament dysfunction in cardiac disease from mice to men. Journal of Muscle Research and Cell Motility. 2008 Dec;29(6-8):189-201. https://doi.org/10.1007/s10974-008-9160-y
Hamdani, Nazha ; De Waard, Monique ; Messer, Andrew E. ; Boontje, Nicky M. ; Kooij, Viola ; Van Dijk, Sabine ; Versteilen, Amanda ; Lamberts, Regis ; Merkus, Daphne ; Dos Remedios, Cris ; Duncker, Dirk J. ; Borbély, A. ; Papp, Z. ; Paulus, Walter ; Stienen, Ger J M ; Marston, Steven B. ; Van Der Velden, Jolanda. / Myofilament dysfunction in cardiac disease from mice to men. In: Journal of Muscle Research and Cell Motility. 2008 ; Vol. 29, No. 6-8. pp. 189-201.
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