More severe cellular phenotype in human idiopathic dilated cardiomyopathy compared to ischemic heart disease

• Published in: Journal of muscle research and cell motility Vol. 31; no. 4; pp. 289 - 301
• Main Authors: Hamdani, Nazha, Borbély, Attila, Veenstra, Sophie P. G. R., Kooij, Viola, Vrydag, Wim, Zaremba, Ruud, dos Remedios, Cris, Niessen, Hans W. M., Michel, Martin C., Paulus, Walter J., Stienen, Ger J. M., van der Velden, Jolanda
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-12-2010; Springer Nature B.V
• Subjects: Actin Cytoskeleton - metabolism; Actin Cytoskeleton - pathology; Animal Anatomy; Biomedical and Life Sciences; Biomedicine; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cardiomyopathies - metabolism; Cardiomyopathies - pathology; Cell Biology; Cells - metabolism; Cyclic AMP-Dependent Protein Kinases - genetics; Cyclic AMP-Dependent Protein Kinases - metabolism; Cyclic AMP-Dependent Protein Kinases - physiology; Heart - physiopathology; Heart Failure - genetics; Heart Failure - metabolism; Heart Failure - physiopathology; Histology; Humans; Life Sciences; Male; Middle Aged; Morphology; Myocardial Ischemia - metabolism; Myocardial Ischemia - pathology; Myocardial Ischemia - physiopathology; Myocardium - metabolism; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Original Paper; Phosphorylation; Proteomics; Receptors, Adrenergic, beta - metabolism; Receptors, Adrenergic, beta-2 - metabolism; Myofilament function; Protein phosphorylation; Cardiomyocyte; Collagen; β-Adrenergic receptor
• ISSN: 0142-4319; 1573-2657
• DOI: 10.1007/s10974-010-9231-8

Activation of the β-adrenergic receptor (βAR) pathway is the main mechanism of the heart to increase cardiac output via protein kinase A (PKA)-mediated phosphorylation of cellular target proteins, and perturbations therein may contribute to cardiac dysfunction in heart failure. In the present study a comprehensive analysis was made of mediators of the βAR pathway, myofilament properties and cardiac structure in patients with idiopathic (IDCM; n = 13) and ischemic (ISHD; n = 10) cardiomyopathy in comparison to non-failing hearts (donor; n = 10) for the following parameters: βAR density, G-coupled receptor kinases 2 and 5, stimulatory and inhibitory G-proteins, phosphorylation of myofilament targets of PKA, protein phosphatase 1, phospholamban, SERCA2a and single myocyte contractility. All parameters exhibited the expected alterations of heart failure, but for most of them the extent of alteration was greater in IDCM than in ISHD. Histological analysis also revealed higher collagen in IDCM compared to ISHD. Alterations in the βAR pathway are more pronounced in IDCM than in ISHD and may reflect sequential changes in cellular protein composition and function. Our data indicate that cellular dysfunction is more severe in IDCM than in ISHD.