Abstract 16021: Effects of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline in Experimental Autoimmune Mocarditis
Background: Acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), a naturally occurring tetrapeptide, prevents autoimmune cardiac dysfunction and remodeling. The mechanism by which this occurs remains unknown. Experimental autoimmune myocarditis (EAM), a T cell-mediated autoimmune disease, is a model of autoimmune cardiac injury. Expression of cytokines and adhesion molecules are a requirement for the development of EAM. We hypothesized that Ac-SDKP prevents autoimmune cardiac injury by reducing T cell response, pro-inflammatory cytokines and adhesion molecules.
Methods and results: EAM was induced by immunization of rats with porcine cardiac myosin, followed by s.c. infusion of vehicle or Ac-SDKP (800 µg.kg-1.d-1) via osmotic minipumps. By 3 weeks post-immunization, we evaluated cell-mediated immunity by delayed-type hypersensitivity, myocardial T helper infiltration by immunohistochemistry and cytokines, chemokines and adhesion molecules were measured with a proteomic array kit. Ac-SDKP prevented increases in 1) Delayed-type sensitivity (EAM, 0.35±0.06 vs EAM + Ac-SDKP, 0.16±0.01 mm), 2) infiltration by T helper cells (148±20 vs 97±17*** CD4 cells/mm2), 3) pro-inflammatory cytokines [Tumor necrosis factor-α (0.98±0.20 vs 0.17±0.03** A.U.); Interleukin (IL)-1β (13.7±2.9 vs 0.29±0.07*** A.U.); IL-17, a T helper type 17 cytokine (1.9±0.3 vs 0.8±0.3* A.U.)], 4) chemokines [cytokine-inducible neutrophil chemoattractant (CINC-1) (1.2±0.2 vs 0.2±0.1***A.U.); IP-10, a T helper type 1 chemokine (1.54±0.23 vs 0.30±0.08*) and 5) Cell adhesion molecules [L-selectin (42.4±4.8 vs 9.1±1.9***) and ICAM-1 (54.1±3.1 vs 19.1±2.8***)].
Conclusion: Prevention of autoimmune cardiac injury by Ac-SDKP is associated with decreased cell-mediated immunity and T helper cell infiltration. Blockade of T helper response by Ac-SDKP is likely due to reduction of pro-inflammatory cytokines that mediate expression of chemokines and cell adhesion molecules. *p<0.05, **p<0.005, and ***p<0.001 EAM vs EAM + Ac-SDKP.
- © 2012 by American Heart Association, Inc.