Fiegle, Dominik
[VerfasserIn]
;
Volk, Tilmann
[AkademischeR BetreuerIn];
Fabry, Ben
[Sonstige Person, Familie und Körperschaft]
Preservation of the Transverse-Tubular System and Excitation-Contraction Coupling in Rodent and Human Ventricular Cardiomyocytes – Effects of Glucocorticoids and Autophagy
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Medientyp:
E-Book;
Hochschulschrift
Titel:
Preservation of the Transverse-Tubular System and Excitation-Contraction Coupling in Rodent and Human Ventricular Cardiomyocytes – Effects of Glucocorticoids and Autophagy
Beschreibung:
Chronic heart failure (HF) is a progressive cardiac disease with a 5-year mortality rate of over 50%. Especially in industrial societies, the prevalence of heart failure is rising with currently over two million affected people in Germany and over 60 million people worldwide. However, therapeutic options are still limited and most patients eventually require heart transplantation to survive. For the development of new therapies, a better understanding of the processes underlying contractile dysfunction in HF is essential. In chronically failing hearts, the transverse tubular system (t-system), a complex network of membrane invaginations of cardiomyocytes, was shown to be severely compromised. Normally, the t-system is very dense and ensures a close apposition of L-type Ca2+ channels (LTCC), located in the cell membrane, with ryanodine receptors (RyR) in the sarcoplasmic reticulum (SR) membrane. The formation of RyR-LTCC junctions promotes a rapid and synchronous rise of cytoplasmic Ca2+, necessary for contraction (excitation-contraction coupling). It is still unclear to which extent loss and remodeling of the t-system contribute to reduced contractility of the heart and vice versa. So far, t system remodeling in human HF was only described in chronically ill patients. However, if t system remodeling may also occur and contribute to dysfunction in acute HF is unknown. Furthermore, despite extensive research, the mechanisms of t-system remodeling are still elusive. Initial experiments showed that glucocorticoid (GC) treatment of animal cardiomyocytes in vitro can prevent t-system loss otherwise observed under control conditions. Therefore, the present study aimed to investigate the t system in human hearts after acute HF. Subsequently, the effects of GC treatment on the t system and EC coupling were studied in model of t-system loss in adult rat cardiomyocytes, and in mouse hearts with cardiomyocyte-specific knockout of the glucocorticoid receptor (GR). It was further investigated if known t system associated ...