Public Defence: Camilla Huse
MSc Camilla Huse at Institute of Clinical Medicine will be defending the thesis “Regulation of immune cells in atherosclerosis and its clinical implications - The role of A-to-I editing and interleukin 6 receptor inhibition” for the degree of PhD (Philosophiae Doctor).
Photo: Ine Eriksen, Universitetet i Oslo.
Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
- First opponent: Professor Paolo Parini, Karolinska Institutet
- Second opponent: Researcher Pieter Goossens, Maastricht University
- Third member and chair of the evaluation committee: Professor Marit Inngjerdingen, University of Oslo
Chair of the Defence
Professor Stine Marie Ulven, Faculty of Medicine, University of Oslo
Senior Researcher Tuva Børresdatter Dahl, Research Institute of Internal Medicine, Oslo University Hospital
Recruitment of immune cells to the developing atherosclerotic plaques is a hallmark in the atherosclerotic process. Immune cell recruitment is also a major factor following acute cardiovascular events in atherosclerosis, such as myocardial infarction and stroke, where there is massive recruitment to the site of injury. To identify treatment targets, there is a need to better understand the immunopathogenic mechanism in the atherosclerotic process and its related clinical implications.
In this thesis, we aimed to: (i) assess the impact of Endonuclease V (EndoV), an enzyme known to cleave adenosine-to-inosine (A-to-I) modified RNA, on the immune cell response in atherogenesis and stroke, and (ii) investigate the effect of tocilizumab, an interleukin-6 (IL-6) receptor inhibitor, on the immune cell levels and responses in patients during ST-elevation myocardial infarction (STEMI).
In human carotid atherosclerotic plaques, we found higher levels of EndoV and A-to-I editing than in non-atherosclerotic arteries. Absence of EndoV gave a reduced atherosclerotic plaque burden, both in lipid content and lesion size, with reduced monocyte recruitment in mice. In addition, abolishment of EndoV seemed to have protective effects on brain damage in a murine hypoxia-ischemic stroke model.
Inhibition of the IL-6 signaling pathway in STEMI patients is beneficial for the patient outcome. This thesis shows that tocilizumab reduced neutrophil and monocyte counts without affecting lymphocyte counts in the circulation following STEMI. Tocilizumab dampened the inflammatory responses in neutrophils with neutrophil degranulation, while monocytes had an upregulation of several cytokine signaling pathways with potential beneficial effects on myocardial remodeling and inflammation. These changes might contribute to the observed improved outcome for the tocilizumab treated patients.
Contact the research support staff.