Universität zu Köln

Schreiber, Charlotte ORCID: 0009-0007-8476-3097 (2025). Characterization of the murine heart and cardiac macrophages after sepsis. PhD thesis, Universität zu Köln.

PDF Dissertation_Charlotte-Schreiber.pdf - Submitted Version Download (4MB)

Abstract

Sepsis is a severe disease that is characterized by a dysregulated host immune response to infection. Even after surviving the life-threatening acute complications, sepsis patients suffer from long-term consequences including a higher risk for cardiovascular events like acute myocardial infarction. The aim of this thesis is to investigate what chronic changes are triggered by sepsis in the murine heart and in tissue resident cardiac macrophages. Cecal Ligation and Puncture (CLP) was used to model sepsis in mice. CLP leads to an increase of blood neutrophils for about 6 weeks. Male and female mice show baseline differences in blood leukocyte count and distribution but react similarly to sepsis with leukocytosis and neutrophilia. Systolic and diastolic heart function and BNP expression in cardiac tissue are not altered seven weeks after CLP, so there is no evidence of impaired cardiac function. Cardiac morphology is also not chronically altered after CLP: There are no signs of cardiac hypertrophy in the histological or echocardiographic analyses. Furthermore, there is no evidence of cardiac fibrosis, as neither an increase in the proportion of fibrosis is observed histologically nor a change in the expression of fibrosis-inducing genes. However, single-cell RNA sequencing reveals a previously unknown cardiac macrophage population after sepsis. This cluster displays prominent inflammatory features. Specifically, genes that drive the attraction of inflammatory leukocytes are upregulated. Whether this newly discovered macrophage population contributes to cardiovascular morbidity and mortality after sepsis is not yet known. Future studies are needed to determine this populations functional relevance.

Item Type:	Thesis (PhD thesis)
Translated title:	Title Language UNSPECIFIED German
Creators:	Creators Email ORCID ORCID Put Code Schreiber, Charlotte UNSPECIFIED https://orcid.org/0009-0007-8476-3097 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-784589
Date:	25 March 2025
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Innere Medizin > Klinik III für Innere Medizin - Kardiologie, Pneumologie, Angiologie und internistische Intensivmedizin
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Cardiac; macrophages English Sepsis English UNSPECIFIED English
Date of oral exam:	25 March 2025
Referee:	Name Academic Title Hoyer, Friedrich Felix Privatdozent Dr. med. Nguemo, Filomain Privatdozent Dr. med.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/78458