Public Defence: Fadila Telarevic Cero
Cand.med. Fadila Telarevic Cero at Institute of Clinical Medicine will be defending the thesis “Hypoxia-Induced Pulmonary Hypertension and Cardiac Dysfunction; The Role of Inflammasomes and related Cytokines” for the degree of PhD (Philosophiae Doctor).
Trial Lecture – time and place
See Trial Lecture.
- First opponent: Professor Jens Erik Nielsen-Kudsk, Aarhus University Hospital, Denmark
- Second opponent: Professor Tomas Mikal Lind Eagan, Department of Clinical Science, University of Bergen
- Third member and chair of the evaluation committee: Professor II Britt Nakstad, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor II Sigrun Halvorsen, Faculty of Medicine, University of Oslo
Professor II Ole Henning Skjønsberg, Faculty of Medicine, University of Oslo
The thesis consists of four papers, which show that innate immunity plays a central role in the development of hypoxia-induced pulmonary hypertension and cardiac dysfunction.
Pulmonary hypertension (PH) is a serious condition that develops as a complication to COPD and other pulmonary diseases associated with hypoxia. PH is associated with increased mortality in lung patients, and there is no effective treatment. The mechanisms leading to PH, which have not been fully elucidated, were the objective of Cero’s research.
The aims of the thesis were to investigate whether inflammasomes are involved in hypoxia-induced pulmonary hypertension. Inflammasomes are proteins regulating innate immunity through activation of the proinflammatory cytokines IL-18 and IL-1β. Our studies showed that hypoxia activates inflammasomes, leading to higher levels of active IL-18 and IL-1β in mice, and, in addition, that the expression of the IL-18 receptor is abundant in lungs, measured by PCR, Western blotting and ELISA. Furthermore, hypoxia induced development of PH, right ventricular remodeling and impaired left ventricular diastolic function, shown by intraventricular pressure measurements, echocardiography and MRI. Absence of inflammasome components in genetically modified mice attenuated the development of PH and generation of IL-18 and IL-1β. By giving IL-18 and IL-12 to healthy mice, the authors found increased levels of emphysema associated enzymes in the lungs.
Hypoxic mice lacking inflammasome components showed reduced right ventricular remodeling. Similar results were obtained by giving wild type mice an IL-18 inhibitor. In addition, improved diastolic function of the left ventricle was observed after such treatment, corresponding with normalization of calcium-handling proteins in the myocardium.
Overall, our studies indicate that inhibition of inflammasome components may be a target for treatment of hypoxia-induced pulmonary hypertension and heart failure.
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