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.
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.
Department of Gastroenterological Surgery, Hangzhou First Hospital, School of Clinical Medicine, Nanjing Medical University, Hangzhou, 310006, China.
Wei
W
Wei
Min
M
Chen
Yanfei
Y
Zhu
Jian
J
Wang
Ping
P
Zhu
Yousheng
Y
Li
Jieshou
J
Li
D000818:Animals; D002908:Chronic Disease; D003314:Corn Oil / Q000008:administration & dosage; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005395:Fish Oils / Q000008:administration & dosage; D006084:Graft Rejection / Q000517:prevention & control*; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*
D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D003314:Corn Oil