title: Involvement of the receptor for advanced glycation end products in liver transplantation.
abstract: OBJECTIVE
  Receptor for advanced glycation end products (RAGE) blockade by a soluble form of RAGE (sRAGE) appears to be protective against hepatocellular death and necrosis after I/R injury. Little is known about the role of the hepatic RAGE, its ligands, and the plasma levels of sRAGE in liver transplantation (LT).
  
  
  METHODS
  This was a prospective study on patients (n = 28) undergoing deceased donor LT. RAGE ligands [the N(epsilon)-carboxy-methyl-lysine (CML) adduct and the high-mobility group box 1 (HMGB1) protein] and sRAGE levels were measured in donors at the time of organ procurement, while in recipients they were tested before surgery (baseline), after graft reperfusion, and on day 1 and 7 posttransplantation. Donors and recipients liver biopsies were collected to assess the transcriptional expression of the full-length RAGE and of its truncated isoform, the endogenous secreted RAGE (esRAGE).
  
  
  RESULTS
  At baseline, CML levels were higher in LT recipients than in donors (p = 0.02), decreased immediately after graft reperfusion (p < 0.0001) and returned to baseline values on day 7. Baseline HMGB1 levels (3.8 ± 2.3 ng/mL) increased after graft reperfusion (39.9±18 ng/mL, p < 0.0001), and returned to baseline values within day 1, while circulating sRAGE decreased significantly on day 7 (p < 0.0001). The graft esRAGE mRNA expression was inversely associated with bilirubin on day 7 (β = -0.62, p = 0.005).
  
  
  CONCLUSIONS
  Early on after LT, there is accumulation of CML and a rapid increase of HMGB1 concurrent with a remarkable decline in circulating sRAGE. The RAGE-ligand axis may also be involved in early graft dysfunction.
authors: Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors: Teresa
authors: T
authors: Navarra
authors: Hepatobiliary surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy.
authors: Paolo
authors: P
authors: De Simone
authors: Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors: Serena
authors: S
authors: Del Turco
authors: Hepatobiliary surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy.
authors: Franco
authors: F
authors: Filipponi
authors: Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors: Giuseppina
authors: G
authors: Basta
mesh_terms: D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005260:Female; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000097:blood; D006801:Humans; D007558:Italy; D008024:Ligands; D016031:Liver Transplantation / Q000009:adverse effects; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000235:genetics; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology; D015398:Signal Transduction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D008024:Ligands; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C048496:N(6)-carboxymethyllysine; D008239:Lysine; D001663:Bilirubin