New findings on heart failure
STED microscopy of an isolated heart muscle cell. Shown is the localisation of the membrane repair protein dysferlin (magenta) along the filigree membrane network within the muscle cell (caveolin-3, green). Cell overview, scale 10 µm.
(c) Sören Brandenburg
Dysferlin protein protects and shapes the membrane of heart muscle cells.
Researchers from the Heart Center of the University Medical Center Göttingen (UMG) led by Priv.-Doz. Dr Sören Brandenburg have identified a protein that plays a central role in the heart’s adaptation to increased stress. The results of the study were published in the renowned journal ‘Circulation Research’.
The heartbeat is carried out by specialized heart muscle cells called cardiomyocytes that can neither divide nor renew themselves. As a result, the loss of a large number of these cells, as in the case of heart muscle diseases or a heart attack, leads to a permanent impairment of the heart muscle. Cardiomyocytes consist of a complex membrane system that is subjected to high mechanical stress during heart muscle contractions. The so-called T-tubule network within the cells, which consists of electrically excitable membrane tubes that are involved in the conduction of electrical signals and the intracellular release of calcium for contraction of the heart muscle, is particularly susceptible. The risk of cardiomyocytes being damaged or dying increases if the heart is subjected to prolonged stress, for example in the case of high blood pressure. The heart has to work harder to pump the blood into the arteries against the increased pressure. The increased workload induces an enlargement of the cardiomyocytes, also known as hypertrophy, which in turn can lead to membrane damage.
Priv.-Doz. Dr Sören Brandenburg, Senior Physician in the Department of Cardiology and Pneumology at the University Medical Center Göttingen (UMG). (c) umg/hzg, Florian Rusteberg
In this context, a team led by Priv.-Doz. Dr. Sören Brandenburg, senior physician in the Department of Cardiology and Pneumology at the University Medical Center Göttingen (UMG), and Prof. Dr. Stephan Lehnart, head of the “Cellular Biophysics and Translational Cardiology” research group at the UMG Heart Center, investigated the protein Dysferlin, which is already known to be associated with muscle diseases. The Göttingen researchers aimed to clarify the specific role of Dysferlin in cardiomyocytes, particularly with regard to the adaptation of the cells to pressure overload. They discovered that the protein plays a decisive role in stabilizing and repairing the cell membranes of cardiomyocytes. “Dysferlin protects cardiomyocytes by rapidly repairing damage to the membrane system caused by periodic contractions and pressure overload, and enables the cells to adapt to increased stress by forming new membrane structures. These findings could pave the way for new therapeutic approaches,” says Dr. Brandenburg, last author of the study. The results were published in the renowned journal ‘Circulation Research’.
About the study
The researchers used high-resolution STED (stimulated emission depletion) microscopy to analyze Dysferlin along membrane structures within cardiomyocytes. This innovative light microscopy allowed them to identify the exact position and function of Dysferlin, especially along the T tubule network. In addition, electron microscopy techniques were used to analyze membrane nanodomains and the connections between different cell organelles responsible for intracellular calcium release. The study was made possible by close collaborations within the framework of the Göttingen Cluster of Excellence “Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells (MBExC)”.
Based on the new findings, the Göttingen scientists are now working on new treatment strategies for patients who suffer from heart failure or are at risk of suffering a heart attack. “The results could enable us to slow down or even stop the progression of heart disease,” says Dr. Brandenburg.
Heart Center of the University Medical Center Göttingen
In the Heart Center of the University Medical Center Göttingen, 14 clinics and institutes as well as the nursing and specialized nursing service of the University Medical Center Göttingen work together in the fields of heart, blood vessels, lungs and kidneys. These organs are particularly closely linked in their function. The clinics and institutes have been brought together to form an interdisciplinary center. This ensures optimal and efficient patient care, research and teaching. The aim of the UMG Heart Center is to provide high-quality medical care in a patient-oriented, open-minded and transparent manner.
Wissenschaftliche Ansprechpartner:
University Medical Center Göttingen, Georg-August-University
Department of Cardiology and Pneumology
Priv.-Doz. Dr. Sören Brandenburg
Robert-Koch-Str. 42a, 37075 Göttingen
Phone +49 551 / 39-63634
soeren.brandenburg@med.uni-goettingen.de
herzzentrum.umg.eu
Originalpublikation:
Nora Josefine Paulke, Carolin Fleischhacker, Justus B. Wegener, Gabriel C. Riedemann, Constantin Cretu, Mufassra Mushtaq Nina Zaremba, Wiebke Möbius, Yannik Zühlke, Jasper Wedemeyer, Lorenz Liebmann, Anastasiia A. Gorshkova, Daniel Kownatzki-Danger, Eva Wagner, Tobias Kohl, Carolin Wichmann, Olaf Jahn, Henning Urlaub, Karl Toischer, Gerd Hasenfuß, Tobias Moser, Julia Preobraschenski, Christof Lenz, Eva A. Rog-Zielinska, Stephan E. Lehnart, Sören Brandenburg: Dysferlin Enables Tubular Membrane Proliferation in Cardiac Hypertrophy. Circulation Research. 2024;135:554–574. DOI: 10.1161/CIRCRESAHA.124.324588
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