Adjudication committee
- First opponent: Consultant Sabiha Gati, St George’s University Hospitals NHS Foundation Trust, UK
- Second opponent: Researcher Anja Bye, NTNU – Norwegian University of Science and Technology,
- Third member and chair of the evaluation committee: Associate professor Jørgen Gravning, University of Oslo
Chair of the Defence
Professor Finn Olav Levy, University of Oslo
Principal Supervisor
Professor I Mathis Korseberg Stokke, University of Oslo
Summary
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. The aim of this Ph.D. was to provide a basis for advice regarding exercise training for patients with a genetic predisposition for HCM.
In a cohort of genotype positive and genotype negative patients with HCM, we used multiple linear regression to compare the amount of exercise performed at a young age (7-20 years old) with diastolic parameters from echocardiography at the time of inclusion, while controlling for effects of age and hypertrophy. We found that exercise during childhood and adolescence was favourably associated with four echocardiographic parameters, i.e. end-diastolic volume, e’, E/e ′, and deceleration time. This was found both in people with hypertrophy and in people with an HCM-causative genetic variant without hypertrophy.
To further understand the effect of exercise initiated prior to disease development, we exposed a mouse model of HCM to treadmill exercise training. The mice exercised for 3 weeks prior to HCM phenotype induction, then the phenotype was induced with cyclosporine A in the feed for 3 weeks paralleled with continued training. Exercised HCM mice had a lower gene expression of several extracellular matrix proteins. However, no changes in fibrosis measured as amount of collagen in tissue sections was observed between exercised and sedentary HCM mice.
In a separate study, using the same mouse model, we investigated two ECM proteins of interest, lumican and collagen, and described the amount and co-localization of these in HCM. In addition to the mouse tissue, we included tissue samples from patients with obstructive HCM, and cell cultures of human foetal cardiac fibroblasts. We observed correlated expression and co-localization of lumican and collagen in both patients and mice with HCM. Addition of lumican to cultured fibroblasts led to thicker, longer and fewer collagen fibres in culture.
The work presented in this thesis provide a basis for further research on the effects of exercise in persons predisposed to HCM, and personalized advice regarding exercise in patients with HCM, especially those with no, or a mild, phenotype.
