CONICET | Buscador de Institutos y Recursos Humanos

Rationale: Myocarditis is commonly associated with cardiotropic infections and has been linked to development of autoimmunity. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring tetrapeptide that prevents inflammation and fibrosis in hypertension and other cardiovascular diseases; however, its effect on autoimmune-mediated cardiac diseases remains unknown. We studied the effects of Ac-SDKP in experimental autoimmune myocarditis (EAM), a model of T cell-mediated autoimmune disease. Objective: To test the hypothesis that Ac-SDKP prevents autoimmune myocardial injury by modulating the immune responses. Methods and Results: Lewis rats were immunized with porcine cardiac myosin and treated with Ac-SDKP or vehicle. In EAM, Ac-SDKP prevented both systolic and diastolic cardiac dysfunction, remodeling as shown by hypertrophy and fibrosis, and cell-mediated immune responses without affecting myosin-specific autoantibodies or antigen-specific T cell responses. In addition, Ac-SDKP reduced cardiac infiltration by macrophages, dendritic cells, and T cells, pro-inflammatory cytokines (IL-1á, TNF-á, IL-2, IL-17) and chemokines (CINC-1, IP-10), cell adhesion molecules (ICAM-1, L-selectin) and matrix metalloproteinases (MMP). Conclusions: Ac-SDKP prevents autoimmune cardiac dysfunction and remodeling without reducing the production of autoantibodies or T cell responses to cardiac myosin. The protective effects of Ac-SDKP in autoimmune myocardial injury are most likely mediated by inhibition of a) innate and adaptive immune cell infiltration and b) expression of pro-inflammatory mediators such as cytokines, chemokines, adhesion molecules and MMPs