After tissue injury, diverse processes contribute to restoration of integrity and function of the injured organ. These processes include inflammation, apoptosis and angiogenesis. During tissue injury, platelets accumulate rapidly at the site of vascular lesions, immediately after the vascular wall - the barrier between intra- and extravascular - is breached. In this locally and temporally defined segment, an intersection point between injury and regeneration exists, where the initial steps for restoration and preservation of an intact and functinal tissue are taken.From the first period of the KFO we know that platelet adhesions receptors as well as released mediators can modulate angiogenesis. Further preliminary work indicates that also other processes contributing to tissue remodelling such as apoptosis can be tailored by platelets, e.g. via mebrane expressed death receptor Fas-L. Furthermore, platelet derived receptors of innate immunity including anaphylatoxin receptors (C5aR) may modulate angiogenesis, but also platelet function. Accordingly, different mechanisms of tissue remodelling such as angiogenesis, apoptosis and inflammation are modulated by platelets. Not only the anaphylatoxins being part of our complement system, but also opsonising complement components C1q and C3 are of relevance. For instance, recent data implicate that the platelet adhesion receptor GPIb mediates an interaction of platelets with active C3. (Verschoor et al., 2011). As apoptotic cells bind complement, this could represent one potential mechanism, how platelets interact with the injured tissue. Moreover, various connection points between platelet activation and the complement system are obvious (Verschoor und Langer, 2013). Thus, the goal of this TP is to define the differential role of platelets for modulation of the aforementioned processes in the different in vivo settings (e.g, hind limb ischemia, myocardial infarction) and to characterize them on a mechanistic level towards mediating platelet effectors such as receptors for apoptosis or inflammation as well as paracrine mediators such as the anti-angiogenic platelet factor 4 (PF-4) elicited from our preliminary work. Translationally, we will also validate candidate proteins originating from results of our patient cohort during the first period of the KFO.