Forsøksdyr: DNA repair, immune system and coagulation in heart failure, stroke and related metabolic disorders

Godkjenningsdato 19.06.2020

Godkjenningsperiode 19.06.2020-18.06.2024

1. Cardiovascular disease (CVD) is the leading cause of mortality. The underlying etiology differ, but usually involves dyslipidemia-induced injuries to the arterial wall, initiating a cascade of inflammatory- and immunological pathways for proper tissue repair. Oxidative stress is a common mechanism during CVD, causing modifications to DNA. Mice deficient in DNA-repair enzymes have altered inflammatory and metabolic pathways, reflecting their role in epigenetic regulation. This project aims to characterize the importance of a fully functional DNA repair system, immune system and/or coagulation cascade in the development and progression of CVD. In addition, we will clarify to what extent coagulation factor V affects the size of thrombus formation.

2. This project include surgical procedures performed under deep anesthesia (moderate stress) in addition to some mildly stressful procedures including pinpricks for blood sampling and non-invasive imaging under anesthesia. Proper analgesic treatment will be provided after surgery, and procedures are scheduled to allow full recovery and no cumulative effects of multiple/repeated procedures. We evaluate the stress level to be "moderate".

3. This project will characterize the importance of a fully functional DNA repair system, immune system and/or coagulation cascade on the development, progression and healing of cardiovascular injury.

4. Mus musculus, this project consists of well-defined work packages. In each experimental group, we will use 10 mice of each relevant genotype. This number allows us to study both genders and will also give us flexibility to terminate suffering animals without compromising the statistical validity. In total, 2470 mice (32 different genotypes).

5. The interplay between individual cells, tissues and organs, and their obvious impact on the whole organism and its phenotype cannot be properly studied outside a living animal. Considerable individual variations are to be expected for cardio-metabolic studies in mice. The number of mice chosen for this project will allow us freedom to terminate animals showing discomfort, sickness or injuries without compromising the statistical validity of our study, and allow us to include both genders. This project will utilize the mice generated from our breeding project (FOTS approval #22322) which will minimize the generation of research animals, and our restrictive breeding plan directs us to only produce the animals needed for our research, and to reduce the number of individuals in any given experiment to a minimum The mice will be checked on a daily basis by KPM staff, and monitored on a weekly basis by project researchers. Anesthesia and analgesia will be properly administered.