In this project we study the functional role of the Danger-Associated Molecular Patterns (DAMPs) and in particular the role of Cyclophilin A (CypA) secreted from platelets and acting on platelets via different receptors during cardiomyopathy and ischaemic heart disease. We will investigate the role of CypA in modulating platelet and immune cell responses that control cardiac remodelling. Moreover, we will address whether acetylation of CypA during myocardial inflammation in platelets boosts CypA effector functions and controls myocardial outcome. In this highly translational project we will furthermore perform a detailed characterization of platelet-DAMPs (including acetylated variants) and their receptors in patients with ischaemic and non-ischaemic cardiomyopathy and develop human antibody-based inhibitors to target platelet-derived DAMPs.
