Treatment of heart failure through exercise training

We have since the start-up of the project had the following main achievements: 1) we have determined that cardiac function can be improved without restoring high energy phosphates (creatine phosphate) and that cardiac function is more related to calcium handling and mitochondrial function, 2) we have established a cause effect relation between calcium handling and miRNAs involved in heart failure and rescued by exercise training and is directly linked to cardiac function, 3) exercise training reduces life-threatening cardiac arrhythmias in an exercise dependent manner and that high intensity is more effective than moderate intensity exercise, 4) the reduction in cardiac arrhythmias is associated with restored electrophysiology and we have established a cause effect relation between a few miRNAs and altered electrophysiology, 5) the research network established is multidisciplinary and has led to strengthened collaboration, new large scale research proposals, new projects and spin-off studies (for instance the discovery of lactate receptors in the brain) and 6) discovery of other novel mechanisms and treatments that is being patented (2 or 3 patents).

Large-scale epidemiological studies demonstrate that aerobic fitness, measured as maximal oxygen uptake, is the single best predictor for future cardiovascular mortality in healthy individuals and in patients with cardiovascular disease. We hypothesise th at both inherited and acquired low level of maximal oxygen uptake initiate detrimental cardiovascular signalling pathways, and that diagnostic as well as therapeutic strategies must be specifically targeted to those pathways. Identification of new biomark ers and positive cardiovascular signalling pathways (through exercise training) will bring forward a potential to establish original and novel therapeutic tools and strategies to treat heart failure and to prevent progression to heart failure, thus contri buting to reduce the burden of cardiovascular and life-style related diseases. Excellence by integration Trondheim, offers a unique research environment for translational research in exercise in medicine, with the new integrated university hospital that is built for multidisciplinary collaboration. Tromsø posses the expertise in cardiac metabolism and mechanoenergetics, and have gained a lot of experience in mice exercise training. The two centres in Oslo are experts in cardiac molecular signalling path ways and electron microscope imaging and protein localisation. Together the centres cover all the way from whole body exercise capacity through cardiac function to molecules, as well as from man to mice. We will establish the underlying cardiovascular m echanisms of how exercise training influence improves cardiac function in heart failure by combining animal models, cell biology and human myocardial specimens. The novelty of the suggested projects is to target heart failure treatment with exercise mimi cking molecular modulation.