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

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 14 months 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.

• Authors: Urszula Mackiewicz, Elżbieta Czarnowska, Magdalena Brudek, Beata Pająk, Monika Duda, Krzysztof Emanuel, Gabor Csanyi, Andrzej Fedorowicz, Elżbieta Grochal, Urszula Tyrankiewicz, Tomasz Skórka, Ulrike Mende, Bohdan Lewartowski, Stefan Chłopicki
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 52 Issue 5 Pg. 978-87 (May 2012) ISSN: 1095-8584 [Electronic] England
• PMID: 22285482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Crystallins
• Cytoskeletal Proteins
• Desmin
• Microtubule-Associated Proteins
• Sodium-Calcium Exchanger
• cryaB protein, rat
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• GTP-Binding Protein alpha Subunits, Gq-G11
• Calcium

Topics

• Analysis of Variance
• Animals
• Calcium (metabolism)
• Calcium Signaling
• Cardiomyopathy, Dilated (metabolism, pathology, physiopathology)
• Cell Size
• Cells, Cultured
• Crystallins (metabolism)
• Cytoskeletal Proteins (genetics, metabolism)
• Desmin (genetics, metabolism)
• Endomyocardial Fibrosis (pathology)
• Female
• GTP-Binding Protein alpha Subunits, Gq-G11 (genetics, metabolism)
• Heart (physiopathology)
• Mice
• Mice, Transgenic
• Microtubule-Associated Proteins (metabolism)
• Myocardial Contraction
• Myocytes, Cardiac (metabolism, physiology)
• Phosphorylation
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (metabolism)
• Sodium-Calcium Exchanger (metabolism)
• Transcription, Genetic
• Ventricular Dysfunction, Left (metabolism, pathology)