Fellowship for Coenen: Platelet Endocytosis and Exocytosis in Wound Healing and Aortic Aneurysm

Scientific summary of research proposal Impaired wound healing, e.g., as a complication underlying diabetes or in aortic aneurysm, is a significant global healthcare problem. Platelets have an active role in at least the initial, haemostatic, phase of wound healing, but less is known about their relevance in subsequent phases, such as inflammation and tissue remodelling. Furthermore, there is very limited evidence of platelet function in aortic aneurysm pathogenesis. To communicate with vascular cells, platelets secrete granules containing cellular mediators. Administration of platelet-rich plasma (PRP) with high concentrations of those factors is clinically used to stimulate wound healing. I aim to gain more understanding into the contribution of platelets, in particular platelet secretion, to wound healing. The proposed research will use mice deficient in endocytosis, exocytosis, and platelet granule biogenesis to investigate these processes in skin wound healing and aortic aneurysm. A full-thickness circular excision skin wounding model and an innovative, but well-characterized aortic aneurysm model will be utilized. In the skin wounding model, PRP will be administered topical or via injection. Successful completion of this research will provide evidence for the significance of the platelet secretion machinery in both physiological (skin wound) and pathological (aortic aneurysm) wound healing and give more insights in the main determinants in PRP-mediated wound healing.