Abstract 3041: The Effect of Adiponectin on the Acute and Chronic Cardiac Allograft Rejection
Background - Adiponectin is an adipose tissue-specific secretory protein and an important anti-inflammatory and anti-atherosclerotic factor. Therefore, we evaluated the role of adiponectin on acute and chronic rejection using adiponectin transgenic mice hearts. Chronic rejection of cardiac allograft is characterized by circumferential and diffuse intimal thickening of graft coronary artery developed several weeks after transplantation in mice.
Methods and Results - In an acute rejection model, BALB/c murine hearts were transplanted into adiponectin sense transgenic mice (Tg-S) (full allomismatch). In a chronic rejection model, B6.C-H-2bm12KhEg (Bm12) murine hearts were transplanted into adiponectin Tg-S mice for examination of graft arterial disease (class II-mismatched combination). In the acute rejection model, survival of cardiac allografts did not differ between the two groups. In the chronic rejection model, quantitative PCR and immunohistochemial staining showed that both adiponectin receptor 1 and 2 expressions were induced in Tg-S mice as recipient. Neointimal hyperplasia was significantly lower in allografts from Tg-S mice as recipients (luminal occlusion, 8.9 %) than in those from control mice (38.5 %, P=0.018). Adiponectin Tg-S mice showed significantly reduced mRNA expression of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin 2 (IL-2), IL-6, IL-10 and monocyte chemoattractant protein-1(MCP-1) by quantitative PCR. Western blot analysis revealed that the protein levels of IFN-γ and MCP-1 were also reduced in adiponectin Tg-S mice.
Conclusion - Adiponectin plays a critical role in cardiac transplantation especially in the development of chronic rejection.