Preserved cardiomyocyte function and altered desmin pattern in transgenic mouse model of dilated cardiomyopathy

Urszula Mackiewicz, Elzbieta Czarnowska, Magdalena Brudek, Beata Pajak, Monika Duda, Krzysztof Emanuel, Gabor Csanyi, Andrzej Fedorowicz, Elzbieta Grochal, Urszula Tyrankiewicz, Tomasz Skórka, Ulrike Mende, Bohdan Lewartowski, Stefan Chłopicki

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Taking advantage of the unique model of slowly developing dilated cardiomyopathy in mice with cardiomyocyte-specific transgenic overexpression of activated Gαq protein (Tgαq *44 mice) we analyzed the contribution of the cardiomyocyte malfunction, fibrosis and cytoskeleton remodeling to the development of heart failure in this model. Left ventricular (LV) in vivo function, myocardial fibrosis, cytoskeletal proteins expression and distribution, Ca 2+ handling and contractile function of isolated cardiomyocytes were evaluated at the stages of the early, compensated, and late, decompensated heart failure in 4-, 12- and 14-month-old Tgαq *44 mice, respectively, and compared to age-matched wild-type FVB mice. In the 4-month-old Tgαq *44 mice significant myocardial fibrosis, moderate myocyte hypertrophy and increased expression of regularly arranged and homogenously distributed desmin accompanied by increased phosphorylation of desmin chaperone protein, αB-crystallin, were found. Cardiomyocyte shortening, Ca 2+ handling and LV function were not altered. At 12 and 14months of age, Tgαq *44 mice displayed progressive deterioration of the LV function. The contractile performance of isolated myocytes was still preserved, and the amplitude of Ca 2+ transients was even increased probably due to impairment of Na +/Ca 2+ exchanger function, while fibrosis was more extensive than in younger mice. Moreover, substantial disarrangement of desmin distribution accompanied by decreasing phosphorylation of αB-crystallin appeared. In Tgαq *44 mice disarrangement of desmin, at least partly related to inadequate phosphorylation of αB-crystallin seems to be importantly involved in the progressive deterioration of contractile heart function.

Original languageEnglish (US)
Pages (from-to)978-987
Number of pages10
JournalJournal of molecular and cellular cardiology
Volume52
Issue number5
DOIs
StatePublished - May 1 2012
Externally publishedYes

Keywords

  • Ca handling
  • Desmin
  • Dilated cardiomyopathy
  • Transgenic mice
  • αB-crystallin

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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    Mackiewicz, U., Czarnowska, E., Brudek, M., Pajak, B., Duda, M., Emanuel, K., Csanyi, G., Fedorowicz, A., Grochal, E., Tyrankiewicz, U., Skórka, T., Mende, U., Lewartowski, B., & Chłopicki, S. (2012). Preserved cardiomyocyte function and altered desmin pattern in transgenic mouse model of dilated cardiomyopathy. Journal of molecular and cellular cardiology, 52(5), 978-987. https://doi.org/10.1016/j.yjmcc.2012.01.008