Trial Lecture – time and place
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Adjudication committee
- First opponent: Professor Nikos Karamanos, Department of Chemistry, University of Patras, Greece
- Second opponent: Professor II Kristian Bartnes, Department of Clinical Medicine, UiT - The Arctic University of Norway
- Third member and chair of the evaluation committee: Professor II Ingebjørg Seljeflot, University of Oslo
Chair of the Defence
Professor II Kjetil Sunde, University of Oslo.
Principal Supervisor
Professor II Theis Tønnessen, University of Oslo
Summary
Cardiac remodeling following pressure overload is seen in patients with hypertension and aortic stenosis, and can lead to heart failure. Cardiac fibrosis is a hallmark of cardiac remodeling. Lumican (LUM) and fibromodulin (FMOD) are structural proteins which are increased in experimental and clinical models of pressure overload and cardiac fibrosis. We have induced pressure overload by aortic banding in genetically-modified mouse models to investigate the role of LUM and FMOD in cardiac remodeling, with focus on cardiac fibrosis.
We have used echocardiography, microscopy and gene or protein expression analysis to look at cardiac function and structure following AB-induced pressure overload. We have shown that total and moderate LUM deficiency attenuates cardiac collagen production and deposition i.e. fibrosis post-AB. Moreover, we showed that total LUM deficiency increases mortality and exacerbates cardiac dilatation and function post-AB, while moderate LUM deficiency does not impact mortality and improves cardiac function. These data indicate that LUM has a gene dosage effect. In vitro cell culture experiments showed that LUM is a pro-fibrotic protein.
Total FMOD deficiency mildly increased cardiac hypertrophy with no effect on mortality or cardiac fibrosis post-AB. In vitro, FMOD had anti-fibrotic characteristics.
In conclusion, LUM and FMOD might be future potential therapeutic targets for diagnosis and treatment of cardiac fibrosis.
Additional information
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