| First Author | Mackiewicz U | Year | 2012 |
| Journal | J Mol Cell Cardiol | Volume | 52 |
| Issue | 5 | Pages | 978-87 |
| PubMed ID | 22285482 | Mgi Jnum | J:318772 |
| Mgi Id | MGI:6858168 | Doi | 10.1016/j.yjmcc.2012.01.008 |
| Citation | Mackiewicz U, et al. (2012) Preserved cardiomyocyte function and altered desmin pattern in transgenic mouse model of dilated cardiomyopathy. J Mol Cell Cardiol 52(5):978-87 |
| abstractText | Taking advantage of the unique model of slowly developing dilated cardiomyopathy in mice with cardiomyocyte-specific transgenic overexpression of activated Galphaq protein (Tgalphaq*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 Tgalphaq*44 mice, respectively, and compared to age-matched wild-type FVB mice. In the 4-month-old Tgalphaq*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, alphaB-crystallin, were found. Cardiomyocyte shortening, Ca(2+) handling and LV function were not altered. At 12 and 14 months of age, Tgalphaq*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 alphaB-crystallin appeared. In Tgalphaq*44 mice disarrangement of desmin, at least partly related to inadequate phosphorylation of alphaB-crystallin seems to be importantly involved in the progressive deterioration of contractile heart function. |
