More severe cellular phenotype in human idiopathic dilated cardiomyopathy compared to ischemic heart disease Nazha HamdaniAttila BorbelySophie P. G. R. VeenstraViola Kooij • Wim VrydagRuud ZarembaCris dos RemediosHans W. M. Niessen • Martin C. MichelWalter J. PaulusGer J. M. StienenJolanda van der Velden

Activation of the b-adrenergic receptor (bAR) pathway is the main mechanism of the heart to increase cardiac output via protein kinase A (PKA)-mediated phosphorylation of cellular target proteins, and perturba- tions therein may contribute to cardiac dysfunction in heart failure. In the present study a comprehensive analysis was made of mediators of the bAR pathway, myofilament properties and cardiac structure in patients with idiopathic (IDCM; n = 13) and ischemic (ISHD; n = 10) cardio- myopathy in comparison to non-failing hearts (donor; n = 10) for the following parameters: bAR 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 bAR 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.