Background: The role of adiponectin (APN), an adipose tissue-specific secretory protein, on chronic rejection after cardiac transplantation in APN-sense transgenic mice (APN-SE) was evaluated.
Methods and Results: Heterotopic cardiac transplantation in major histocompatibility complex class II-mis-matched mice was performed. B6 center dot C-H-2(bm12)KhEg (Bm12) hearts were transplanted into APN-SE, and allografts were harvested at 8 weeks after transplantation. Quantitative polymerase chain reaction (PCR) and immunohistochemical staining showed that the expression of both AdipoR1 and AdipoR2 was induced in APN-SE recipients. Neointimal hyperplasia was significantly decreased in allografts transplanted into APN-SE (luminal occlusion, 8.9 +/- 2.2%) compared to those transplanted into controls (49.4 +/- 10.5%; P=0.011). APN-SE showed significantly reduced mRNA levels of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-6, and monocyte chemoattractant protein-1 (MCP-1) by quantitative PCR. Western blot analysis revealed that the protein levels of IFN-gamma and MCP-1 were reduced in APN-SE recipients. Proliferation of smooth muscle cells stimulated with activated T cells was suppressed by APN addition, and this effect was canceled by treatment with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor.
Conclusions: APN plays a critical role in the attenuation of chronic rejection by suppressing inflammatory cytokine and chemokine expression and enhancing APN receptor expression. APN plays a beneficial role in reducing the progression of cardiac allograft vasculopathy through the AMPK pathway. (Circ J 2011; 75: 2005-2012)