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Kardiologie
ResearchCardiologyInternal MedicineUniversity departmentsMedical University of Graz

Molecular and cellular mechanisms of heart failure

Our research focuses on the fundamental mechanisms of cardiac aging and heart failure with preserved ejection fraction (HFpEF) – the most common and still growing chronic cardiovascular disease in the elderly. We aim to validate caloric restriction mimetics as effective molecular candidates and therapeutic interventions against cardiovascular aging, cardiometabolic syndrome, and HFpEF. We combine whole body physiological and cell-/tissue-specific molecular approaches by using aged or appropriate transgenic animal models and human liquid and myocardial biopsies from failing and non-failing donors.

Our team pioneered the application of caloric restriction mimetics in cardiovascular medicine by demonstrating the cardioprotective effects of the natural autophagy-inducer, spermidine, which is currently being tested in hypertensive patients.

Our group made a significant contribution to the international fight against HFpEF by demonstrating that boosting NAD+ metabolism with nicotinamide or other NAD+ precursors might become a viable therapy for HFpEF.

We found that the relationship between cardiac insulin/insulin-like growth factor-1 (IGF-1) receptor signaling and healthspan is not linear as currently viewed, but rather biphasic and age-dependent. This finding reveals how fine regulation of the cardiac IGF1 receptor signaling in the course of aging can promote health and longevity.

Going forward, our new flagship projects INTERACD+ and VASC-HEALTH, respectively, focus on the mechanisms responsible for exercise- and NAD+-mediated protection from cardiometabolic risk and aim at defining actionable mechanistic targets based on autophagy and vascular attrition, which are until now not amenable to therapeutic interventions.

Team Simon Sedej

Team Simon Sedej

Our efforts are directed towards advancing research in the area of improving healthspan and addressing key processes in metabolic control of the heart that are impacted by obesity, hypertension, and aging.

Contact and Group leader

Assoz. Prof. Priv.-Doz. Dr. rer. nat.
Simon Sedej 
T: +43 316 385 72742
E: simon.sedej(at)medunigraz.at
Simon Sedej
Research profile

Alina Stockner  
PhD student
Alina Stockner

Anila Varghese 
PhD student
Anila Varghese

Daksh Verma 
PhD student
Daksh Verma

Viktoria Trummer-Herbst 
Lab Manager
Viktoria Trummer-Herbst

Team

  • Mahmoud Abdellatif, MD, PhD (Assistant Professor)
  • Alina Stockner, PhD student
    Her project focuses on the regulation of lipid alterations in heart failure with preserved ejection fraction.
  • Verma Daksh, PhD student
    His project focuses on heart-specific effects of exercise and NAD+ metabolism in the setting of cardiometabolic risk.
  • Viktoria Trummer-Herbst, biomedical assistant
  • Anila Varghese, PhD student
    Her project focuses on targeting growth factor signaling to promote cardiovascular health in aging.

Alumni

  • Nika Barbara Pravica, MD (BioTechMed lab rotation)
  • Jan Schafmeister, MD
  • Hendrik Jöst, MD
  • Simon Kraler, MD
  • Jan Esser, MD
  • Alina Humnig, MSc
  • Julia Voglhuber, MSC (BioTechMed lab rotation)
  • Felix Renneberg, MD
  • Martin Wernhart, MD
  • Marinko Matovina, MD
  • Clemens Reiter, MD
  • Corinna Simonini, MD
  • Isabella Windhager, MD
  • Georg Arnstein, MD
  • Eva Thon-Gutschi, MSc

National collaborations

  • Frank Madeo (University of Graz)
  • Tobias Eisenberg (University of Graz)
  • Renate Schreiber (University of Graz)
  • Rolf Breinbauer (Technical University of Graz)
  • Kathrin Thedieck (University of Innsbruck)
  • Andreas Koeberle (University of Innsbruck)
  • Stefan Kiechl (Medical University of Innsbruck)
  • Manuel Mayr (Medical University Wien/King’s College London)

International collaborations

  • Guido Kroemer (University of Sorbonne, France)
  • Christian Mühlfeld (Medical School Hannover, Germany)
  • Kari Alitalo (University of Helsinki, Finnland) 
  • Junichi Sadoshima (New Jersey Medical School, USA)
  • Abhinav Diwan (St. Louis Washington University, USA)
  • Wolfgang Linke (University of Münster, Germany)
  • Julie McMullen (Baker Heart Institute, Australia)
Leuchtturmprojekt INTERACD+
VASC-HEALTH - Flagship Projekt
VASC-HEALTH - neue Therapien
VASC-HEALTH - ORF wissenswert

Ten most important publications

1. Abdellatif M, […], Kroemer G, and Sedej S (2022). Fine-tuning cardiac insulin-like growth factor 1 receptor signaling to promote health and longevity. Circulation. 145(25): 1853-1866. doi:10.1161/CIRCULATIONAHA.122.059863.

2. Abdellatif M, […], Kroemer G, and Sedej S (2021). Nicotinamide for the treatment of heart failure with preserved ejection fraction. Science Translational Medicine. 13 (580), eabd7064. doi:10.1126/scitranslmed.abd7064.

3. Eisenberg T, Abdellatif M, […], Kroemer G, Sedej S, and Madeo F (2016). Cardioprotection and life span extension by the natural polyamine spermidine. Nature Medicine. 22(12): 1428–1438. doi:10.1038/nm.4222. #equally contributed and corresponding authors.

4. Abdellatif M, Sedej S, and Kroemer G (2021). NAD+ metabolism in cardiac health, aging and disease. Circulation. 144(22):1795-1817. doi:10.1161/CIRCULATIONAHA.121.056589.

5. Ljubojevic-Holzer S and Kraler S, […], Sedej S (2021). Loss of autophagy protein ATG5 impairs cardiac capacity in mice and humans through diminishing mitochondrial abundance and disrupting Ca2+ cycling. Cardiovascular Research. cvab112. doi:10.1093/cvr/cvab112.

6. Abdellatif M and Sedej S (2022).Metabolic therapy for managing heart failure with preserved ejection fraction. Journal of Molecular and Cellular Cardiology. 168:68-69. doi: 10.1016/j.yjmcc.2022.04.009.

7. Abdellatif M, Sedej S, Carmona-Gutierrez D, Madeo F, and Kroemer G (2018). Autophagy in Cardiovascular Aging. Circulation Research. 123(7): 803–824. doi:10.1161/CIRCRESAHA.118.312208.

8. Abdellatif M, […], and Sedej S. (2020) Autophagy in cardiovascular health and disease. Progress in Molecular Biology and Translational Science. 172:87-106. doi:10.1016/bs.pmbts.2020.04.022.

9. Sedej S, […], and Pieske B. (2014). Subclinical abnormalities in sarcoplasmic reticulum Ca2+ release promote eccentric myocardial remodeling and pump failure death in response to pressure overload. Journal of the American College of Cardiology. 63(15):1569-79. doi:10.1016/j.jacc.2013.11.010.

10. Sedej S, […], and Pieske B. (2010). Na+-dependent SR Ca2+ overload induces arrhythmogenic events in mouse cardiomyocytes with a human CPVT mutation. Cardiovascular Research. 87(1):50-9. doi: 10.1093/cvr/cvq007

Full publications list (Pubmed): https://pubmed.ncbi.nlm.nih.gov/?term=sedej+s&sort=date

Nicotinamide for the treatment of heart failure with preserved ejection fraction

in Science Translational Medicine, 2021