Down-regulation of vascular HMGB1 and RAGE expression by n-3 polyunsaturated fatty acids is accompanied by amelioration of chronic vasculopathy of small bowel allografts

作者：Wei, Wei; Chen, Min; Zhu, Yanfei; Wang, Jian; Zhu, Ping; Li, Yousheng^*; Li, Jieshou

来源：Journal of Nutritional Biochemistry, 2012, 23(10): 1333-1340.

DOI：10.1016/j.jnutbio.2011.08.002

• n-3 polyunsaturated fatty acids
• Chronic allograft vasculopathy
• Receptor for advanced glycation end-products
• High mobility group box 1
• Small bowel transplantation

Chronic allograft rejection, which is manifested as chronic allograft vasculopathy (CAV), continues to refrain the long-term success of small bowel transplantation (SBTx). The pathway mediated by the receptor for advanced glycation end products (RAGE) and its ligand, high mobility group box-1 (HMGB1), may contribute to the pathogenesis of CAV given that they were involved in the process of allograft rejection. n-3 polyunsaturated fatty acids (PUFAs), which have been discovered to attenuate CAV, may have potential impacts on this pathway. The present study investigated whether n-3 PUFAs attenuated CAV via the regulation of the HMGB1-RAGE pathway in a chronic rejection model of rat SBTx. We revealed that the expression of HMGB1 and RAGE was increased in CAV-bearing vessels as well as endothelial cells isolated from these vessels. Oral administration of fish oil with high levels of n-3 PUFAs following SBTx significantly reduced the HMGB1 and RAGE expression, which coincided with the amelioration of CAV. In contrast, feeding of corn oil that contained low levels of n-3 PUFAs had no favorable effects on CAV development and failed to decrease the HMGB1 and RAGE expression. These results indicate that protective effects of n-3 PUFAs on allograft vessels exist via down-regulation of the HMGB1-RAGE pathway.

• 出版日期2012-10
• 单位南京医科大学; 南京大学; 南京中医药大学