More severe cellular phenotype in human idiopathic dilated cardiomyopathy compared to ischemic heart disease.
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.
Institute for Cardiovascular Research, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
Nazha
N
Hamdani
Attila
A
Borbély
Sophie P G R
SP
Veenstra
Viola
V
Kooij
Wim
W
Vrydag
Ruud
R
Zaremba
Cris
C
Dos Remedios
Hans W M
HW
Niessen
Martin C
MC
Michel
Walter J
WJ
Paulus
Ger J M
GJ
Stienen
Jolanda
J
van der Velden
D008841:Actin Cytoskeleton / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology*; D002477:Cells / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D011943:Receptors, Adrenergic, beta; D018343:Receptors, Adrenergic, beta-2; D000099211:Phospholamban