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Chronic inflammatory reactions directed against cells within the vascular wall or the myocardium are key elements in the pathogenesis of cardiovascular diseases. Although myocarditis is a rather frequent cause of death in young adults, the lack of knowledge about its course and the differential contribution of innate and adaptive immune res-ponses has hampered diagnosis and treatment. In particular, the mechanisms underlying the progression from myocarditis to dilated cardiomyopathy (DCM) have remained elusive. Likewise, chronic vascular rejection (transplant arteriosclerosis) of solid organ grafts is still the major reason for retransplantion in organ transplantation. Therefore, it is important to determine the molecular and cellular key factors involved in these cardiovascular immunopathological diseases. The major aim of this research project is to determine the critical immunopatho-logical factors involved in cardiovascular inflammatory processes. Particular emphasis will be put on the involvement of CD4+ T helper cells in the process of autoimmune myocarditis/DCM. Furthermore, we will determine the contribution of CD4+ T cells in the process of CD8+ T cell-mediated endothelial injury. The planned studies will utilize novel transgenic mouse models to understand the factors that influence the decision making process between T cell activation versus T cell tolerization during autoimmune myocarditis and chronic transplant rejection. We anticipate that the planned studies will not only extend our knowledge on the basic immunological mechanisms that mediate chronic inflammatory processes within the cardiovascular system, but will facilitate the development of intervention and prevention strategies aimed to control chronic immune activation in cardiovascular diseases.

Funded through SNF contribution 130823