Public Defence: Hilde Elisabeth Lang Orrem
Cand.med. Hilde Elisabeth Lang Orrem at Institute of Clinical Medicine will be defending the thesis “Innate immunity in acute coronary syndromes. Focus on complement” for the degree of PhD (Philosophiae Doctor).
Trial Lecture – time and place
See Trial Lecture.
- First opponent: Head of laboratory Marina Noris, Mario Negri Institute for Pharmacological Research, Milan, Italy
- Second opponent: Group leader Christoph Schmidt, Institute of Pharmacology of Natural Products & Clinical, Pharmacology, Ulm University, Germany
- Third member and chair of the evaluation committee: Professor II Guttorm Haraldsen, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor Emeritus Ingvar Jarle Vaage, Faculty of Medicine, University of Oslo
Professor II Tom Eirik Mollnes, Faculty of Medicine, University of Oslo
The innate immune system plays a crucial role in the sterile inflammation seen in the wake of a myocardial infarction (MI). Inflammation is essential for cardiac repair, but can also contribute to enhanced damage to the tissue and is involved in adverse remodeling with risk of heart failure (HF) development. Complement, IL-6 and IL-1 are important mediators of inflammation.
The aim of the thesis was to evaluate the innate immune system with focus on the complement cascade and the IL-1- signaling system in acute coronary syndromes, particularly with respect to disease severity and adverse cardiac remodeling. Blood samples from different cohorts of patients with acute coronary syndromes and myocardial infarction were evaluated with enzyme-linked immunosorbent assays or PCR. The effect of complement inhibition on infarct size, left ventricular function and inflammation was tested in an experimental trial.
Complement activation was increased in patients following a MI with the highest activation found in the most severely affected patients. Heart function measured with echocardiography correlated with complement activation in the most severely affected patients. Complement inhibition led to reduced infarct size and improved cardiac function in the experimental trial.
We further found interactions between complement and both IL-6 and IL-1. Inhibiting IL-6 signaling led to lower expression of complement receptors mediating inflammation (C5aR1 and C5aR2). Inhibiting complement in an experimental model of myocardial infarction almost abolished IL-1 in the infarcted area.
Negative regulators of IL-1 were found to be associated with markers of myocardial injury and HF development in patients with MI.
Overall, the studies show that complement plays an important role in tissue injury and infarct size following MI and further in adverse remodeling and HF development. Targeting the complement cascade could be relevant supplementary treatment to established reperfusion therapy.
Contact the research support staff.