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dc.contributor.advisor Maier, Lars S. Prof. Dr.
dc.contributor.author Reichle, Jochen
dc.date.accessioned 2016-12-12T10:40:31Z
dc.date.available 2016-12-27T23:51:10Z
dc.date.issued 2016-12-12
dc.identifier.uri http://hdl.handle.net/11858/00-1735-0000-002B-7CD5-5
dc.language.iso deu de
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc 610 de
dc.title Der Einfluss des AT2-interacting Protein 1 (ATIP1) auf die Kontraktilität und den Kalziumstoffwechsel von ventrikulären Herzmuskelzellen de
dc.type doctoralThesis de
dc.title.translated The Influence of AT2-interacting Protein 1 (ATIP1) on Contractility and Calcium Metabolism of ventricular Heart Muscle Cells de
dc.contributor.referee Niebert, Marcus PD Dr.
dc.date.examination 2016-12-20
dc.description.abstracteng In the context of this work, ATIP1 knockout mice demonstrated for the first time that both the AT2 receptor and the AT2-interacting protein 1 (ATIP1), which interacts with this receptor, have a functional influence on contractility and electromechanical coupling on isolated ventricular heart muscle cells. Experiments were carried out by means of epifluorescence microscopy to two groups of mice of different age. Neither the young nor the older mice caused the loss of ATIP1 a higher heart-to-body weight ratio and thus cardiac hypertrophy. In the young animals, no differences between ATIP1-KO mice and the WT control could be found in the functional measurements under basal conditions. In contrast, experiments with older mice under basal conditions show increased contractility as well as increased cell relaxation in ATIP1-KO mice. This comparatively positive inotropic effect can best be explained by an increased fractional SR calcium efflux. An increased SERCA2a activity is considered for faster cell relaxation because the NCX function did not differ in the measurements of this work. Interestingly, stimulation with Ang II resulted in a significantly stronger contraction in WT mice cells and a significantly reduced contractility in ATIP1-KO mice. Analogously, a faster relaxation of the WT cells were shown under the influence of Ang II. The results of the measurements with the AT2 agonist CGP42112A were analogous to the measurements with Ang II. This observation shows that ATIP1 is a relevant component in an over the AT2 receptor mediated cascade, which has an important influence on the electromechanical coupling of the heart. In order to adjust the overall performance of the ATIP1-KO mice in relation to that of the WT mice, I stimulated the β-adrenergic pathway with isoprenaline in a further series of measurements. However, there were no differences between ATIP1-KO- and WT-animals. This means that the loss of ATIP1 has no effect on the β-adrenergic signaling pathway. The pharmacological therapy of cardiac insufficiency with ACE inhibitors and AT1 antagonists has a high priority. The results of this work provide an increased insight into the role of the less understood AT2 receptor and ATIP1 on the cardiac level. Thus, new pharmacological approaches to the therapy and prophylaxis of cardiac insufficiency could be found. de
dc.contributor.coReferee Oppermann, Martin Prof. Dr.
dc.subject.eng ATIP1 de
dc.subject.eng AT2 receptor de
dc.subject.eng epifluorescence microscopy de
dc.subject.eng CGP42112A de
dc.subject.eng isolated heart cells de
dc.identifier.urn urn:nbn:de:gbv:7-11858/00-1735-0000-002B-7CD5-5-3
dc.affiliation.institute Medizinische Fakultät de
dc.subject.gokfull Medizin (PPN619874732) de
dc.subject.gokfull Innere Medizin - Allgemein- und Gesamtdarstellungen (PPN619875747) de
dc.description.embargoed 2016-12-27
dc.identifier.ppn 874354668

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