title: Effect of adiponectin on cardiac allograft vasculopathy.
abstract: 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.
  
  
  RESULTS
  Heterotopic cardiac transplantation in major histocompatibility complex class II-mismatched mice was performed. B6.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)-γ, tumor necrosis factor (TNF)-α, 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-γ 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.
authors: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Takashi
authors: T
authors: Ishihara
authors: Go
authors: G
authors: Haraguchi
authors: Masanori
authors: M
authors: Konishi
authors: Hirokazu
authors: H
authors: Ohigashi
authors: Kiyomi
authors: K
authors: Saito
authors: Yasuko
authors: Y
authors: Nakano
authors: Mitsuaki
authors: M
authors: Isobe
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D006084:Graft Rejection / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016027:Heart Transplantation; D006965:Hyperplasia; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058426:Neointima / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054419:Receptors, Adiponectin / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D052242:Adiponectin; D047428:Protein Kinase Inhibitors; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; D055372:AMP-Activated Protein Kinases