Book of Abstracts - New Frontiers 2022

Abstracts of oral presentations

NEUREGULIN-1 ATTENUATES DEVELOPMENT OF CARDIAC AND KINDEY DYSFUNCTION IN A RAT MODEL OF CHRONIC KIDNEY DISEASE

A. Kiss 1 , M. Sárközy 2 , E. Acar 1 , Z. Kovács 2 , S. Watzinger 1 , F. Márványkövi 2 , G. Szücs 1 , A. Siska 3 , I. Földesi 3 , A. Kriston 4 , P. Horváth 4 , G. Cseri 5 , B. Kővári 5 , L. Szabó 1 , D. Abraham 6 , T. Csont 2 , B. Podesser 1 1 Ludwig Boltzmann Institute for Cardiovascular Research at Center for Biomedical Research and Translational Surgery, Medical University of Vienna, Vienna, Austria; 2 MEDICS Research Group, Department of Biochemistry, Interdisciplinary Center of Excellence, University of Szeged, Szeged, Hungary; 3 Department of Laboratory Medicine, Faculty of Medicine, University of Szeged, Szeged, Hungary; 4 Synthetic and Systems Biology Unit, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary; 5 Department of Pathology, Faculty of Medicine, University of Szeged, Szeged, Hungary; 6 Center for Anatomy and Cell Biology, Medical University Vienna, Vienna, Austria Chronic kidney disease (CKD) is uremic cardiomyopathy characterised by left ventricular hypertrophy, (LVH), diastolic dysfunction and cardiac fibrosis. Inflammation and dysregulation of endothelium-derived neuregulin- 1β (NRG - 1β) sig nalling are known contributors to heart failure with different etiologies. Here, we aimed to clarify 1) the impact of CKD on the expression of NRG-1 and 2) recombinant human neuregulin- 1 β (rhNRG - 1β) treatment to alleviate cardiac and renal dysfunction in a rat model of CKD. Adult male Wistar rats were randomised into 3 groups: i) sham-operated group (iv. saline; 0.5 mL/kg/day), ii) 5/6-nephrectomy-induced CKD group (iv. saline; 0.5 mL/kg/day), and iii) rhNRG- 1β -treated (iv. 10 μg/kg/day) CKD group. Treatme nts were administered daily from week 3 for 10 days. Ten weeks after the operations, cardiac and renal NRG- 1β expressions were significantly reduced in CKD compared to the sham-operated group. In CKD, rhNRG-1 treatment markedly improved renal function and serum LDL cholesterol levels, suggesting its reno- and atheroprotective effects. In CKD, rhNRG- 1β treatment alleviated concentric LVH, diastolic dysfunction and cardiac fibrosis as well as macrophage infiltration. Furthermore, rhNRG- 1β treatment significan tly reduced expression of molecular markers of fibrosis, inflammation and oxidative-stress in LV tissue, cardiac fibroblast and isolated cardiomyocytes. In conclusion, the rhNRG- 1β treatment improved both uremic cardiomyopathy and renal function. Therefore , rhNRG- 1β may represent a novel promising agent in prevention and therapy for uremic cardiomyopathy.

Keywords: heart failure, chronic kidney disease, neuregulin-1, cardioprotection

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