title: Receptor for advanced-glycation end products: key modulator of myocardial ischemic injury.
abstract: BACKGROUND
  The beneficial effects of reperfusion therapies have been limited by the amount of ischemic damage that occurs before reperfusion. To enable development of interventions to reduce cell injury, our research has focused on understanding mechanisms involved in cardiac cell death after ischemia/reperfusion (I/R) injury. In this context, our laboratory has been investigating the role of the receptor for advanced-glycation end products (RAGE) in myocardial I/R injury.
  
  
  RESULTS
  In this study we tested the hypothesis that RAGE is a key modulator of I/R injury in the myocardium. In ischemic rat hearts, expression of RAGE and its ligands was significantly enhanced. Pretreatment of rats with sRAGE, a decoy soluble part of RAGE receptor, reduced ischemic injury and improved functional recovery of myocardium. To specifically dissect the impact of RAGE, hearts from homozygous RAGE-null mice were isolated, perfused, and subjected to I/R. RAGE-null mice were strikingly protected from the adverse impact of I/R injury in the heart, as indicated by decreased release of LDH, improved functional recovery, and increased adenosine triphosphate (ATP). In rats and mice, activation of the RAGE axis was associated with increases in inducible nitric oxide synthase expression and levels of nitric oxide, cyclic guanosine monophosphate (cGMP), and nitrotyrosine.
  
  
  CONCLUSIONS
  These findings demonstrate novel and key roles for RAGE in I/R injury in the heart. The findings also demonstrate that the interaction of RAGE with advanced-glycation end products affects myocardial energy metabolism and function during I/R.
authors.affiliation: Division of Surgical Science, Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Loredana G
authors.initials: LG
authors.lastname: Bucciarelli
authors.forename: Michiyo
authors.initials: M
authors.lastname: Kaneko
authors.forename: Radha
authors.initials: R
authors.lastname: Ananthakrishnan
authors.forename: Evis
authors.initials: E
authors.lastname: Harja
authors.forename: Larisse K
authors.initials: LK
authors.lastname: Lee
authors.forename: Yuying C
authors.initials: YC
authors.lastname: Hwang
authors.forename: Shulamit
authors.initials: S
authors.lastname: Lerner
authors.forename: Soliman
authors.initials: S
authors.lastname: Bakr
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.forename: Wu
authors.initials: W
authors.lastname: Qu
authors.forename: Teodoro
authors.initials: T
authors.lastname: Gomez
authors.forename: Yu Shan
authors.initials: YS
authors.lastname: Zou
authors.forename: Shi Fang
authors.initials: SF
authors.lastname: Yan
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Ramasamy
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000032:analysis; D004734:Energy Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000172:deficiency / Q000502:physiology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D015854:Up-Regulation
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D006152:Cyclic GMP