title: Blocking the receptor for advanced glycation end product activation attenuates autoimmune myocarditis.
abstract: BACKGROUND
  The Receptor for Advanced Glycation End Products (RAGE) is a pattern recognition receptor for endogenous ligands, and is associated with various inflammatory diseases. However, the role of RAGE activation in myocarditis has yet to be examined. The potential role of RAGE in the development of experimental autoimmune myocarditis (EAM) and the effect of RAGE blocking in attenuating the inflammation in the EAM was investigated.
  
  
  RESULTS
  EAM was evoked in Lewis rats by immunization with porcine cardiac myosin. Soluble RAGE (sRAGE) was injected to block RAGE activation. Echocardiogram, histological, and immunohistochemical examinations were conducted on days 21 and 42. In rats with EAM, RAGE expression in cardiac tissue was prominent on day 21. Rats administered sRAGE during the early antigen-priming phase showed marked attenuation in acute and chronic inflammation compared with untreated rats. RAGE expression was significantly reduced in rats treated in the early phase. However, sRAGE administration, after the initial antigen-priming phase, failed to ameliorate EAM development.
  
  
  CONCLUSIONS
  RAGE expression was significantly increased in the heart during EAM. Blocking RAGE activation with sRAGE during the early antigen-priming phase reduced acute and chronic inflammation and improved cardiac function. In contrast, blocking RAGE after the early phase did not attenuate EAM development. These results imply that RAGE is involved in regulating innate immune responses during the early phase of myocarditis development.
authors.affiliation: Department of Cardiology, CHA Bundang Medical Center, CHA University.
authors.forename: Woo-In
authors.initials: WI
authors.lastname: Yang
authors.forename: Dajeong
authors.initials: D
authors.lastname: Lee
authors.forename: Da Lyung
authors.initials: DL
authors.lastname: Lee
authors.forename: Sung-Yu
authors.initials: SY
authors.lastname: Hong
authors.forename: Sang-Hak
authors.initials: SH
authors.lastname: Lee
authors.forename: Seok-Min
authors.initials: SM
authors.lastname: Kang
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Choi
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000276:immunology*; D007113:Immunity, Innate; D008297:Male; D009205:Myocarditis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000276:immunology; D013552:Swine
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic