Blocking the receptor for advanced glycation end product activation attenuates autoimmune myocarditis

Woo In Yang, Dajeong Lee, Da Lyung Lee, Sung Yu Hong, Sang Hak Lee, Seok Min Kang, Dong Hoon Choi, Yangsoo Jang, Se Hoon Kim, Sungha Park

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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. Methods and 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.

Original languageEnglish
Pages (from-to)1197-1205
Number of pages9
JournalCirculation Journal
Volume78
Issue number5
DOIs
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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