Clin Res Cardiol 101, Suppl 1, April 2012

P996 - Modulation of the myocardial expression of Neuregulin-1 and its receptor ErbB4 in patients with chronic heart failure

J. Rothkopf1, S. Reinwand2, S. Kreth2, I. Kaczmarek1, F. Weis2, A. Beiras-Fernandez3

1Herzchirurgische Klinik und Poliklinik, Klinikum der Universität München, Campus Großhadern, München; 2Klinik für Anästhesiologie, Klinikum der Universität München, Campus Großhadern, München; 3Klinik für Thorax-, Herz- und Thorakale Gefäßchirurgie, Universitätsklinikum Frankfurt am Main, Frankfurt am Main;

Introduction: Neuregulin-1 (NRG-1) is a cardioactive paracrine growth factor released by microvascular endothelial cells that has cardioprotective effects in animal models of heart failure. ErbB4 is a member of the ErbB family that serve as receptor for NRG-1. Administration of NRG-1 has been shown to improve LV function in chronic heart failure (CHF) experimental models. Our aim was to determine whether CHF is associated with changes in expression and distribution of NRG-1 and its receptor erbB4 in human myocardium. Material and methods: Expression of Neuregulin-1 and its receptor ErbB4 was assessed by means of real-time PCR on left ventricle and atrial myocardium of patients with CHF undergoing heart transplantation (n=12). All patients gave informed consent. Biopsies (n= 40) of the explanted hearts were obtained and divided according to the anatomical origin (Left Ventricle, Atrium). A control group consisting of left ventricle (n=5) and right atrium (n=5) muscle biopsies from patients with good ejection fraction (EF > 65%) was designed. Results: Expression of ErbB4 was significantly down-regulated in the left ventricle of patients in comparison to the control group and up-regulated in atrium (CHF vs. healthy ventricle: 8.66E-05 vs. 3.35E-04; CHF vs. healthy atrium: 1.20E-04 vs. 6.20E-05). Expression of Neuregulin-1 was significantly up-regulated in the left ventricle and in both left and right atrium of patients in comparison to the control group (CHF vs. healthy ventricle: 2.4E-04 vs. 2.45E-05; CHF vs. healthy atrium: 5.34E-04 vs. 2.83E-04). Conclusions: Neuregulin-1 and its receptor ErbB4 show different expression patterns in patients with end-stage CHF and in patients with conserved EF. Reduced heart function originated a higher expression of Neuregulin-1 in cardiomyocytes and a decrease on the expression of ErbB4. Our results confirm the modulation of NRG-1/ErbB4 signalling in human heart failure.

Clin Res Cardiol 101, Suppl 1, April 2012 Zitierung mit Vortrags- oder Posternummer s.o. DOI 10.1007/s00392-012-1100-6

http://www.abstractserver.de/dgk2012/ft/abstracts/P996.htm