TY - JOUR
T1 - Preserved cardiomyocyte function and altered desmin pattern in transgenic mouse model of dilated cardiomyopathy
AU - Mackiewicz, Urszula
AU - Czarnowska, Elzbieta
AU - Brudek, Magdalena
AU - Pajak, Beata
AU - Duda, Monika
AU - Emanuel, Krzysztof
AU - Csanyi, Gabor
AU - Fedorowicz, Andrzej
AU - Grochal, Elzbieta
AU - Tyrankiewicz, Urszula
AU - Skórka, Tomasz
AU - Mende, Ulrike
AU - Lewartowski, Bohdan
AU - Chłopicki, Stefan
N1 - Funding Information:
This work has been supported by the Polish Ministry of Science and Higher Education [grant numbers N N518419733 , N N401015135 , N N401114533 ]. MK. Duda was supported by the Foundation for Polish Science grant HOM/2008/2B . An expert technical contribution of Alicja Protasowicka is gratefully acknowledged. We thank Anna Kowalczyk and Anna Obruśnik for their excellent support with the breeding of Tgαq ⁎ 44 mice.
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Ca handling
KW - Desmin
KW - Dilated cardiomyopathy
KW - Transgenic mice
KW - αB-crystallin
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U2 - 10.1016/j.yjmcc.2012.01.008
DO - 10.1016/j.yjmcc.2012.01.008
M3 - Article
C2 - 22285482
AN - SCOPUS:84859646682
SN - 0022-2828
VL - 52
SP - 978
EP - 987
JO - Journal of molecular and cellular cardiology
JF - Journal of molecular and cellular cardiology
IS - 5
ER -