PhD Scientific Days 2023

Budapest, 22-23 June 2023

Molecular Sciences - Posters K

Inflammasome activity in the skeletal muscle and heart of rodent models for Duchenne muscular dystrophy

Zsófia Onódi, MD, PhD1,2,3, Petra Lujza Szabó, PhD4, Dániel Kucsera, PharmD1,2,3, Péter Pokreisz, PhD4, Christopher Dostal, MSc4, Karlheinz Hilber, PhD5, Gavin Y Oudit, MD, PhD6, Bruno K. Podesser, MD, PhD4, Péter Ferdinandy, MD, PhD1,7, Zoltán V. Varga, MD, PhD1,2,3, Attila Kiss, PhD4

1 Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
2 HCEMM-SE Cardiometabolic Immunology Research Group, Semmelweis University, Budapest, Hungary
3 MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Semmelweis University, Bu-dapest, Hungary
4 Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research and Transla-tional Surgery, Medical University of Vienna, Austria
5 Department of Neurophysiology & Neuropharmacology, Center for Physiology & Pharmacology, Medical University of Vienna, Vienna, Austria
6 Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada
7 Pharmahungary Group, Szeged, Hungary

Text of the abstract

Background: Duchenne muscular dystrophy (DMD) is characterized by wasting of muscles that lead to difficulty moving and premature death mainly from heart failure. Glucocorticoids are applied in the management, supporting the hypothesis that inflammation may be driver as well as target. However, the inflammatory mechanisms during progression of cardiac and skeletal muscle dysfunction is still not well-characterized.
Aim: Our objective was to characterize the inflammasomes activation in myocardial and skeletal muscle in rodent model of DMD.
Methods: Gastrocnemius and heart samples were collected from mdx mice and DMDmdx rats (3 and 9-10 months). Inflammasome sensors and effectors were assessed by immunoblotting. Histology was used to assess leukocyte infiltration and cardiac fibrosis.
Results: In gastrocnemius a tendency towards elevation of gasdermin D irrespective of the age of animals was observed. The adaptor protein ASC was elevated in mdx mouse skeletal muscle and heart. Increased cleavage of cytokines (interleukin-1 beta and -18) was observed in the skeletal muscle of DMDmdx rats. Inflammasome sensor or cytokine expression was not changed in the tissue samples of mdx mice. The presence of leukoyte infiltration and fibrosis in both skeletal muscle and heart tissue was confirmed in both DMD models.
Conclusion: In conclusion, inflammatory responses are distinct between skeletal muscle and heart in relevant models of DMD. Inflammation tends to decrease over time, supporting the clinical observations that the efficacy of anti-inflammatory therapies might be more prominent in early stage.