Lymphatic Endothelium in Terminal Heart Failure and after Heart and Lung Transplantation

Abstract

The primary goal of the conducted research was to analyse the role of lymphatic endothelial cell in heart failure as well as in the setting of heart and lung transplantation. Our observations of lymphatic phenotype after heart and lung transplantation in human patients are the first of their kind and provide the evidence, that acute allograft rejection is associated with significant changes of lymphatic endothelial phenotype. In experimental studies, we demonstrated that ischemia-reperfusion injury activated the lymphatic endothelium in cardiac allografts. The process was mediated by interaction in the VEGF-C and VEGFR-3 axis and had direct consequences for the development of alloimmune responses. Furthermore, specific perioperative single-dose VEGF-C inhibition demonstrated beneficial effects on lymphatic vessel activation, antigen-presenting cell transport and subsequent alloimmune responses in cardiac allografts. The results of the studies, thus, demonstrate the significance of VEGF-C-VEGFR-3 signaling in promotion of alloimmunity and suggest VEGF-C/D inhibiting strategies as an alternative clinically feasible lymphatic vessel targeted immunomodulatory approach.

No Finnish or Swedish abstract available for the reason of the author´s origin.