Neuregulin-1β Improves Uremic Cardiomyopathy and Renal Dysfunction in Rats

Márta Sárközy; Simon Watzinger; Zsuzsanna Z A Kovács; Eylem Acar; Fanni Márványkövi; Gergő Szűcs; Gülsüm Yilmaz Lauber; Zsolt Galla; Andrea Siska; Imre Földesi; Attila Fintha; András Kriston; Ferenc Kovács; Péter Horváth; Bence Kővári; Gábor Cserni; Tibor Krenács; Petra Lujza Szabó; Gábor Tamás Szabó; Péter Monostori; Karin Zins; Dietmar Abraham; Tamás Csont; Peter Pokreisz; Bruno K Podesser; Attila Kiss

doi:10.1016/j.jacbts.2023.03.003

Neuregulin-1β Improves Uremic Cardiomyopathy and Renal Dysfunction in Rats

JACC Basic Transl Sci. 2023 May 31;8(9):1160-1176. doi: 10.1016/j.jacbts.2023.03.003. eCollection 2023 Sep.

Authors

Márta Sárközy^{1

2}, Simon Watzinger³, Zsuzsanna Z A Kovács^{1

2}, Eylem Acar³, Fanni Márványkövi^{1

2}, Gergő Szűcs^{1

2}, Gülsüm Yilmaz Lauber³, Zsolt Galla⁴, Andrea Siska⁵, Imre Földesi⁵, Attila Fintha⁶, András Kriston^{7

8

9}, Ferenc Kovács^{7

8

9}, Péter Horváth^{7

8

9}, Bence Kővári¹⁰, Gábor Cserni¹⁰, Tibor Krenács⁶, Petra Lujza Szabó³, Gábor Tamás Szabó³, Péter Monostori⁴, Karin Zins¹¹, Dietmar Abraham¹¹, Tamás Csont^{1

2}, Peter Pokreisz³, Bruno K Podesser³, Attila Kiss³

Affiliations

¹ MEDICS Research Group, Department of Biochemistry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
² Interdisciplinary Center of Excellence, University of Szeged, Szeged, Hungary.
³ Ludwig Boltzmann Institute for Cardiovascular Research at Center for Biomedical Research and Translational Surgery, Medical University of Vienna, Vienna, Austria.
⁴ Metabolic and Newborn Screening Laboratory, Department of Pediatrics, Albert Szent-Györgyi Medical School, University of Szeged, Hungary.
⁵ Department of Laboratory Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
⁶ Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
⁷ Synthetic and Systems Biology Unit, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary.
⁸ Single-Cell Technologies Ltd, Szeged, Hungary.
⁹ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
¹⁰ Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
¹¹ Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.

Abstract

Chronic kidney disease is a global health problem affecting 10% to 12% of the population. Uremic cardiomyopathy is often characterized by left ventricular hypertrophy, fibrosis, and diastolic dysfunction. Dysregulation of neuregulin-1β signaling in the heart is a known contributor to heart failure. The systemically administered recombinant human neuregulin-1β for 10 days in our 5/6 nephrectomy-induced model of chronic kidney disease alleviated the progression of uremic cardiomyopathy and kidney dysfunction in type 4 cardiorenal syndrome. The currently presented positive preclinical data warrant clinical studies to confirm the beneficial effects of recombinant human neuregulin-1β in patients with chronic kidney disease.

Keywords: cardiac fibrosis; chronic kidney disease; left ventricular hypertrophy; recombinant human neuregulin-1β; uremic cardiomyopathy.