Yousheng Li, Wei Wei, Yanfei Zhu, Jian Wang, Jieshou Li

Nanjing University, Nanjing, People's Republic of China

Chronic vasculopathy(CV), characterized by diffuse mesenteric intimal hyperplasia, is one of typical feature of CR. The second part of the study of the study has revealed that n-3PUFAs significantly ameliorate CV. However, the underlying mechanisms remain to be investigated. HMGB1, a unclear protein, belongs to damage-associated molecular pattern molecules. It, physiologically located at nucleus, is released to extracellular environment and binds to Toll-like receptor (TLR) and RAGE in pathological conditions. TLR and RAGE are pattern-recognition receptors, which mediate non-specific inflammatory responses. These responses not only contribute to development of atherosclerosis and diabetic vasculopathy, but enhance specific allograft rejection. The present study is to investigate the expression of HMGB1 and REGE in CV and their alterations by n-3 PUFAs.

Through immunohistological fluorescence and Western blot, we detected the expression of HMGB1 and RAGE in mesenteric vessels, and found that their expression was elevated in CV. As compared to PBS group, the FO group had significantly lower HMGB1 and RAGE expression while their expression was not changed in the CO group. Via fluorescent immunostaining, we also detected the expression of the two molecules in the endothelial cells isolated from graft mesentery. The results were in accordance with those seen from graft mesenteric vessels.

In conclusion, HMGB1 and RAGE expression was elevated in CV. It suggested that would contribute to the CV development. Their expression was reduced by n-3 PUFAs, which might be associated with the protective effect n-3 PUFAs on CV.

Keywords: n-3 polyunsaturated fatty acids, high mobility group box-1, receptor for advanced glycation end product, mesenteric endothelial cell, chronic vasculopathy of small bowel allograft, orthotopic small bowel transplantation, chronic rejection.