Einfluss des lymphatischen Systems auf die Entwicklung einer Herzinsuffizienz durch Erhöhung der Nachlast

Sasse, André

dc.contributor.advisor	Dressel, Ralf Prof. Dr.
dc.contributor.author	Sasse, André
dc.date.accessioned	2017-12-04T09:19:15Z
dc.date.available	2017-12-06T23:50:11Z
dc.date.issued	2017-12-04
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0023-3F97-4
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-6583
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	610	de
dc.title	Einfluss des lymphatischen Systems auf die Entwicklung einer Herzinsuffizienz durch Erhöhung der Nachlast	de
dc.type	doctoralThesis	de
dc.title.translated	Effect of lymphoid cells on the progression of pressure overload-induced heart failure	de
dc.contributor.referee	Dressel, Ralf Prof. Dr.
dc.date.examination	2017-12-06
dc.description.abstracteng	Previous studies described an effect of T lymphocytes on the development of heart failure caused by an increased afterload. In this thesis, the involvement of all types of lymphocytes in the development of heart failure after transverse aortic constriction (TAC) was analyzed by comparing wild type (C57BL/6), Rag2-/- mice lacking B and T cells, and Rag2-/-γc-/- mice lacking B, T and innate lymphoid cells (ILCs), which include classical natural killer (NK) cells but also the only recently discovered ILC1, ILC2 and ILC3 populations. An infiltration of hematopoietic cells accompanied by myocardial fibrosis and cardiac hypertrophy was found within three days and up to 10 weeks after TAC in the three mouse strains. Most of the cells were myeloid cells. The wild type mice showed an infiltration also of B and T cells into the myocardium after TAC. Pro-inflammatory cytokines, such as IL-6, were elevated in the serum after TAC in C57BL/6 and Rag2-/-γc-/- mice. How, no significant deviation of the cytokine profile was found in Multiplex-Cytokine-Assays when wild type and Rag2-/-γc-/- mice were compared. Echocardiography was performed before and 1, 4, and 8 weeks after TAC or sham operation. A cardiac hypertrophy could be shown within one week in all three mouse strains. However, the ventricular dilation was more pronounced in wild type and Rag2-/- than in Rag2-/-γc-/- mice. In contrast to C57BL/6 and Rag2-/- mice that developed a heart failure with reduced ejection fraction (HFrEF), Rag2-/-γc-/- mice appeared to display a heart failure with preserved ejection faction (HFpEF) after TAC. Thus, neither B cells nor T cells were required for the development of heart failure in response to an increased afterload but ILCs seem to affect the phenotype of the heart failure. HFpEF is a recently defined disease entity with high mortality and few therapeutic options. Rag2-/-γc-/- mice appear to be an animal model for HFpEF and the comparison with Rag2-/- mice suggests that ILCs are important effector cells in the progression of heart failure.	de
dc.contributor.coReferee	Fischer, Thomas Horst PD Dr.
dc.subject.eng	heart failure	de
dc.subject.eng	transverse aortic constriction	de
dc.subject.eng	innate lymphoid cells	de
dc.subject.eng	heart failure with reduced ejection fraction	de
dc.subject.eng	heart failure with preserved ejection faction	de
dc.subject.eng	HFrEF	de
dc.subject.eng	HFpEF	de
dc.subject.eng	Cytokine	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0023-3F97-4-9
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Immunologie / Allergologie / Umweltmedizin / Medizinische Ökologie - Allgemein- und Gesamtdarstellungen (PPN619875445)	de
dc.subject.gokfull	Kardiologie (PPN619875755)	de
dc.description.embargoed	2017-12-06
dc.identifier.ppn	1007157119

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