Assessing novel treatment strategies for experimental myocardial infarction and atherosclerosis

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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. These processes are involved in both tissue damage and repair. This project will assess the potential of a novel, synthetic peptide to dampen the inflammatory processes responsible for tissue damage in both myocardial infarction and atherosclerosis. In the second part, we will establish a novel mouse model for atherosclerosis regression studies.

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 is part of an innovation study to assess the potential of a novel peptide to dampen the inflammatory response which drives tissue damage in myocardial infarction and atherosclerosis. There is a constant need for new treatment strategies to combat the increasing incidences of cardiovascular disorders worldwide. In the second part, this project will establish a novel mouse model for atherosclerosis regression studies. The gold standard for such studies is aorta transplantation. There is therefore an unmet need for an easy-to-use model with milder impact on animal welfare.

4. Mus musculus, this project consists of well-defined work packages. The number of animals included is based on experience and our general ambition to not discriminate between genders. In addition, the number also give us flexibility to terminate suffering animals without compromising the statistical validity. In total, 225 mice.

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..