Emerging Perspectives in TransplantationExperimental transplantationEffects of Monocyte Chemotactic Protein-1 and Nuclear Factor of Kappa B Pathway in Rejection of Cardiac Allograft in Rat

•We established the rat models of different rejection degrees.•The expression level of MCP-1 was positively correlated with the inflammatory degree of the cardiac allograft.•The degree of rejection can be estimated by detecting the level of MCP-1 in cardiac allografts.•PDTC can significantly prevent the rejection of cardiac allografts by inhibiting MCP-1 expression via the suppression of the NF-κB pathway.•The myocardial fibrosis or CAV can represent the function of the cardiac allograft, as an important index of chronic rejection.

BackgroundGraft 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.MethodsHeterotopic 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.ResultsThe 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).ConclusionThese 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.