The role of Ca/calmodulin dependent protein kinase II (CaMKII) in the heart for triggering and maintenance of atrial fibrillation in diabetes mellitus

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Diabetes mellitus (DM) is a worldwide epidemic that causes numerous cardiovascular diseases and increases mortality in patients. DM is also an independent risk factor for atrial fibrillation (AF), while the mechanisms of DM-associated AF are poorly understood. Along with the clinical importance of DM concerning increased morbidity and mortality, DM is also a pivotal social and economic problem. My previous studies and work from other groups suggest CaMKII plays a critical role in triggering and maintenance of AF. Therefore, in this research proposal I would like to study the role of oxidized CaMKII as compared to mitochondrial CaMKII for AF triggering and maintenance in DM. I will use a range of mouse models, but also human atrial heart tissue. To further decipher the mechanistic pathways I will use both in-vitro and in-vivo techniques. My hypotheses include defects of intracellular Ca homeostasis and upstream-mechanisms of CaMKII activation, but also adverse atrial remodeling, which promotes the maintenance of AF. My translational research proposal aims at identifying unknown disease pathways as well as first applications of new therapeutic concepts.