Die Untersuchung der putativen Mechanosensor-Komponenten Melusin und T cap und deren Einfluss auf die elektromechanische Kopplung im Kardiomyozyten bei adaptiver und maladaptiver Hypertrophie
An analysis of the suspected mechanosensor proteins Melusin and T-Cap in the hypertrophic cardiomyocytes and their influence in the EC-coupling
von Johannes Vogt
Datum der mündl. Prüfung:2017-09-27
Erschienen:2017-09-06
Betreuer:Prof. Dr. Lars S. Maier
Gutachter:PD Dr. L. Zelarayán-Behrend
Gutachter:Prof. Dr. Thomas Meyer
Dateien
Name:JVogt.pdf
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Zusammenfassung
Englisch
An important research topic is the analysis of hypertrophic signals in cardiomyocytes leading to heart failure. There are suspected intracellular mechanosensors in the signal transduction. The proteins Melusin and T-cap are parts of the cytoskeleton with hints for an important role in hypertrophic signaling. T-cap could be in interaction with the potassium channel Iks. The knockout (KO) of T-cap leads to dilatative cardiomyopathy and long-QT-syndrome. The T-cap mouse was examined with fluorescence microscopy and patch-clamp technic. Hypothesis was to find delayed repolarization in the T-cap-KO. The results did not show an influence in EC-coupling or repolarization in the mouse cardiomyocyte. Melusin connects beta1-integrines and sarcomeres. Melusin-transgen mice showed protective effects in pressure overloaded (TAC) hypertrophy. Hypothesis was to find this effect in pathological (TAC/MI) and physiological (Swim) stress models. The MI-mouse showed two weeks after intervention a better contractility and relaxation time, maybe due to higher calcium-sensitivity. TAC and Swim mouse model did not. The NCX-function was elevated in all three interventions. In conclusion, the specific cardiac stress seems to be responsible for the protective effect in the melusin-transgen model.
Keywords: heart failure