Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Peter Libby, Brigham and Women’s Hospital and Harvard Medical School, USA
- Second opponent: Professor Irene Marthe Lang, Medical University of Vienna, Austria
- Third member and chair of the evaluation committee: Professor Ivar Sjaastad, University of Oslo
Chair of the Defence
Professor II Thor Edvardsen, University of Oslo
Principal Supervisor
Post Doc Ragnhild Helseth, Oslo University Hospital
Summary
Despite advances in the treatment of coronary artery disease, our understanding of atherothrombosis is incomplete. Increasing evidence highlights immune cells as key players in this complex process. Neutrophils, the most abundant white blood cells, as well as neutrophil extracellular traps (NETs) seem to be important in atherosclerotic plaque progression and thrombosis.
NETs are filamentous structures that are expelled from neutrophils, and consist of DNA, histones, and neutrophil-derived proteins. Beyond their antimicrobial effects, NETs are thought to be proinflammatory and prothrombotic. Therefore, the main hypothesis of this thesis was that higher NETs levels would be associated with a detrimental clinical outcome in coronary artery disease. The aim was to assess prognostic value by quantifying the circulating NETs markers double-stranded DNA (dsDNA), myeloperoxidase-DNA, and citrullinated histone 3, and exploring any associations to clinical endpoints.
In chronic coronary syndrome, dsDNA levels were higher amongst men, smokers, patients with a previous myocardial infarction and metabolic syndrome. DsDNA was further associated with a higher endpoint rate and poorer survival in the long-term follow-up of both patients with chronic coronary syndrome and STEMI, respectively. DsDNA is albeit potentially also released through processes unrelated to NETs.
The thesis presented for the first time how NETs levels evolve in the setting of acute heart failure after STEMI. Patients with cardiogenic shock had significantly higher levels of dsDNA and citrullinated histone 3. The involvement of NETs in myocardial recovery could not be confirmed, perhaps owing to the small sample size.
The results underscore the relevance of NETs in patients with coronary artery disease. However, inconsistent observations between the measured NETs markers impeded firm conclusions regarding prognostic value, and further research is required to identify possible clinical applications.
Additional information
Contact the research support staff.