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: Professor Jérôme Leroy, Université Paris-Saclay, France
- Second opponent: Professor Robert Feil, Eberhard Karl University of Tübingen, Germany
- Third member and chair of the evaluation committee: Researcher Cathrine Rein Carlson, University of Oslo
Chair of the Defence
Professor Mathis Korseberg Stokke, University of Oslo
Principal Supervisor
Associate Professor Kjetil Wessel Andressen, University of Oslo
Summary
Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome that accounts for roughly half of all heart failure cases and affects a rapidly growing patient population worldwide. HFpEF is strongly linked to comorbidities such as obesity, hypertension, and diabetes and is characterized by diastolic dysfunction, cardiac stiffening, hypertrophy, and fibrosis. Despite its prevalence, treatment options remain limited, largely due to an incomplete understanding of the underlying mechanisms.
In our work, we specifically address how cyclic GMP (cGMP) signaling is compartmentalized within cardiomyocytes and whether targeting this pathway through C-type natriuretic peptide (CNP) could represent a therapeutic strategy in HFpEF.
The work combines in vivo mouse models of HFpEF with advanced molecular techniques, including FRET-based biosensors, to study localized cGMP dynamics in cardiomyocytes. Using these approaches, we demonstrated that long-term CNP treatment improves diastolic function, reduces stiffness, and mitigates hypertrophy and fibrosis in HFpEF. Furthermore, novel insights were gained into cGMP regulation within subcellular compartments such as the mitochondria, sarcoplasmic reticulum, and myofilaments. Distinct regulation by phosphodiesterases was identified, and compartment-specific responses to natriuretic peptides were revealed, highlighting the complexity of intracellular signaling.
Together, these findings advance the understanding of compartmentalized cGMP signaling in the heart and support the therapeutic potential of CNP in HFpEF.
Additional information
Contact the research support staff.