Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Associate Professor Monika Gladka, Amsterdam University Medical Centers, Netherlands
- Second opponent: Professor Saumya Das, Harvard Medical School, USA
- Third member and chair of the evaluation committee: Associate Professor Kjetil Wessel Andressen, University of Oslo
Chair of the Defence
Professor Sandip Kanse, University of Oslo
Principal Supervisor
Researcher Gustavo José Justo da Silva, University of Oslo
Summary
Heart failure (HF) is a major cause of hospitalization and death worldwide, and its prevalence is expected to increase. Heart failure with preserved ejection fraction (HFpEF) is particularly challenging because it is a complex, multisystem disease influenced by obesity, diabetes, hypertension, and kidney dysfunction. Current approaches have important limitations, creating a need for reliable biomarkers and new therapeutic targets.
This thesis investigated the role of microRNAs (miRNAs) in HF diagnosis, prognosis, and pathophysiology, with a focus on HFpEF. A combination of large-scale clinical analyses and experimental studies using established animal models was applied. The clinical analyses showed that specific circulating miRNAs are associated with HF and can help distinguish HFpEF from other forms of HF. Combining miRNAs with conventional biomarkers improved diagnostic performance. Several miRNA patterns were also associated with HF development, hospitalization, and death, suggesting their potential value for risk prediction.
Complementary preclinical studies identified panels of circulating miRNAs that reflect cardiac dysfunction and may serve as diagnostic biomarkers. Animal models resembling the different HF etiologies enabled the identification of miRNAs altered in cardiac tissue and associated with cardiac hypertrophy, diastolic dysfunction, and kidney abnormalities. Additionally, it has been shown that the miRNA expression pattern depends on the underlying disease and comorbidities. Lastly, we demonstrated that these miRNAs are involved in processes relevant to HF, including TGF-β, Hippo, FOXO, and NF-κB signalling.
Overall, this thesis supports miRNAs as promising biomarkers for HF diagnosis and prognosis and provides evidence that they may contribute to HFpEF mechanisms. The findings demonstrate the value of combining clinical and experimental approaches to identify disease-relevant miRNAs. Further studies are needed to validate these findings and support their translation into clinical practice.
Additional information
Contact the research support staff.