title: Effects of Monocyte Chemotactic Protein-1 and Nuclear Factor of Kappa B Pathway in Rejection of Cardiac Allograft in Rat.
abstract: BACKGROUND
  Graft rejection is a key obstacle to successful heart transplantation. We sought to investigate the expression and role of monocyte chemotactic protein-1 (MCP-1) in rejection of cardiac allografts, as well as the role of the nuclear factor of kappa B (NF-κB) pathway.
  
  
  METHODS
  Heterotopic cervical heart transplantation was performed using a modified cuff-technique. Recipient rats (n = 12) underwent acute rejection (AR) without any treatment (AR group). The remaining rats (3 groups; n = 12/group) were treated with Cyclosporine A (CsA; CsA group), immunologic tolerance (IT; IT group), and pyrrolidine dithiocarbamate (PDTC; NF-κB inhibitor; PDTC group). We studied the inflammatory infiltration and myocardial fibrosis of cardiac allografts with hematoxylin-eosin (HE) and Masson staining, and detected the expression of MCP-1 by immunohistochemistry and Western blotting. Cardiac allograft vasculopathy (CAV) also was evaluated using van Gieson staining.
  
  
  RESULTS
  The survival time of the PDTC group (142.37 ± 24.28 days) was significantly longer than that of the AR group (6.54 ± 2.47 days; P = .00073) and the CsA group (93.51 ± 20.17 days; P = .0052). Myocardial fibrosis and CAV in the PDTC group were significantly attenuated compared with the CsA group (P < .01). The expression of MCP-1 in the IT group was markedly lower than in the other 3 groups (P < .05). The expression of MCP-1 in the PDTC group was also significantly lower than the CsA group (1.15 ± 0.27 vs 1.58 ± 0.17; P = .016).
  
  
  CONCLUSIONS
  These findings suggest that the expression level of MCP-1 could be monitored to reflect the severity of cardiac allograft rejection. PDTC can significantly prevent the rejection of cardiac allografts by inhibiting MCP-1 expression via the suppression of the NF-κB pathway.
authors: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, China.
authors: X
authors: X
authors: Bai
authors: Department of Cardiology, The 5th People's Hospital Of Jinan, Jinan, China.
authors: Z
authors: Z
authors: Qi
authors: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, China. Electronic address: songgm@sdu.edu.cn.
authors: G
authors: G
authors: Song
authors: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, China.
authors: X
authors: X
authors: Zhao
authors: Department of Cardiovascular Surgery, Beijing Aortic Center, An Zhen Hospital, Capital Medical University, Beijing, China.
authors: H
authors: H
authors: Zhao
authors: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, China.
authors: X
authors: X
authors: Meng
authors: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, China.
authors: C
authors: C
authors: Liu
authors: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, China.
authors: W
authors: W
authors: Bing
authors: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, China. Electronic address: yanwenbi1@126.com.
authors: Y
authors: Y
authors: Bi
mesh_terms: D064591:Allografts; D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism*; D016027:Heart Transplantation; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D018932:Chemokine CCL2; D016328:NF-kappa B