Molecular And Gene Therapy For Organ Transplantation: Targeting Of Lymph Angiogenesis As a New Immunomodulatory Approach In Heart Transplantation

• Applicant: Privatdozent Alexey Dashkevich, Ph.D.
• Subject Area: Cardiac and Vascular Surgery
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 201579246

Heart transplantation is the best option for patients with terminal heart failure. The organ rejection represents a dangerous clinical complication after the operation. The occurrence of episodes of treated rejection is a risk factor for coronary allograft vasculopathy and development of chronic rejection, which is the major limitation of long-term survival. The rejection related socio-economic consequences are severe: lower survival rate, prolonged hospitalisation and intensive costs for rejection treatment.Although the currently used immunosuppressive drugs effectively inhibit proliferation of alloreactive T cells, they have metabolic, infectious, renal and malignant side effects and still do not completely prevent the development of acute cardiac allograft rejection and are not able to prevent chronic rejection. For this reason, the search for further alternative approaches in rejection therapy remains relevant.Lymphatic network and chemokine-mediated signals are essential for leukocyte traffic during the initial steps of alloimmune response. We are aiming to determine the role of lymphatic vessels and their principal growth signaling pathway in alloimmune rejection. For this purpose we intent to investigate the details of lymphatic vessel activation after heart transplantation in small animals, and to describe the effect of cardiac allograft lymphatic vessel activation on immune cell traffic and development of acute and chronic rejection. This new knowledge may provide the theoretical basis for testing therapeutic targeting of lymphatic vessel activation in cardiac allografts.We suggest that intervening with lymph angiogenesis and so with leukocyte traffic can represent a novel lymphatic vesseltargeted immunomodulatory therapy for cardiac allograft rejection. Development of a new immunomodulatory therapeutic approach for treating cardiac allograft rejection by intervening with post transplant lymphatic vessel activation is the primary goal of the project.

• DFG Programme: Research Fellowships
• International Connection: Finland
• Host: Karl Lemström, Ph.D.