Die unterschätzte Rolle von Thrombozyten bei der Herztransplantation

Transplant arteriosclerosis, the hallmark feature of chronic rejection, is still the leading cause of late mortality after heart transplantation. Current immunosuppressive therapies do not prevent the formation of transplant arteriosclerosis. This review focuses on the role of platelets in heart transplantation, in particular on the pathogenetic role of activated platelets in the formation of vascular lesions after heart transplantation. In addition, a therapeutic strategy is introduced in an experimental aortic allograft model. Using this model, it was shown that monotherapy with clopidogrel reduced the formation of transplant arteriosclerosis significantly. Cellular analysis of the aortic transplant revealed fewer numbers of infiltrating dendritic cells (CD205+) and macrophages (F4/80+) following application of clopidogrel, whereas T-cells within the graft were unaltered. In a final set of experiments it was shown that a combination of platelet- and mTOR-inhibition can dramatically reduce the development of transplant arteriosclerosis. As a consequence of these encouraging results a multicenter-study was initiated throughout Germany to investigate the benefit of this new therapeutic strategy in clinical practice.