Digital Public Defence: Hedda Benedicte Hoel
Cand.med. Hedda Benedicte Hoel at Institute of Clinical Medicine will be defending the thesis “Inflammasome activation, gut microbiota and comorbidities in HIV and COVID-19” for the degree of PhD (Philosophiae Doctor).
Photo: Amalie Huth Hovland, UiO
The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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.
Digital Trial Lecture – time and place
- First opponent: Professor Magnus Gisslen, University of Gothenberg, Sahlgrenska Hospital, Sweden
- Second opponent: Associate Professor Bjørn Blomberg, University of Bergen, Haukeland University Hospital
- Third member and chair of the evaluation committee: Professor Tone Tønjum, University of Oslo
Chair of the Defence
Professor II Olav Dalgard, University of Oslo
Associate Professor Marius Trøseid, University of Oslo
Despite antiretroviral treatment people with HIV still have a lower life expectancy and increased risk of non-communicable comorbidities such as cardiovascular diseases. Several mechanisms including chronic immune activation, inflammation and traditional risk factors contribute, but exact mechanisms remain elusive. Altered gut microbiota is seen in many diseases including HIV, and lately also COVID-19. Tryptophan metabolism through the kynurenine pathway is of importance in the interplay between microbiota and the immune system. Inflammasome activation is central in the atherogenic pathogenesis, and leads to the release of the proinflammatory cytokines IL-1 and IL-18. These cytokines are tightly regulated, and markers of this activation can be analyzed in plasma.
This thesis aimed to elucidate mechanisms related to microbiota, inflammasome activation and cardiovascular involvement in the RNA viral diseases HIV and Covid-19.
The main findings were that patients that had both HIV and Type 2 diabetes had a reduced gut microbial diversity, higher levels of inflammation and a higher Kynurenine/Tryptophan ratio. Also, tryptophan metabolism was associated with endothelial dysfunction. Furthermore, in a nested case control study, markers of IL-1 activity predicted myocardial infarction in HIV patients up to 10 years before the insult, suggesting the IL-1 system could be an important target for preventive intervention.
In Covid-19 disease respiratory symptoms are most common, but the gut and heart is also affected. In a longitudinal observational study of hospitalized patients with COVID-19, those with cardiac involvement had higher levels of LPS binding Protein and IL-18 suggesting a gut-heart axis in Covid-19, possibly involving inflammasome activation, but further studies are needed.
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