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 journalArticle

6 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

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Myocarditis
Inflammation
Antigens
Advanced Glycosylation End Product-Specific Receptor
Cardiac Myosins
Pattern Recognition Receptors
Innate Immunity
Immunization
Swine
Ligands

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

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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. 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.",
author = "Yang, {Woo In} and Dajeong Lee and Lee, {Da Lyung} and Hong, {Sung Yu} and Lee, {Sang Hak} and Kang, {Seok Min} and Choi, {Dong Hoon} and Yangsoo Jang and Kim, {Se Hoon} and Sungha Park",
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Blocking the receptor for advanced glycation end product activation attenuates autoimmune myocarditis. / Yang, Woo In; Lee, Dajeong; Lee, Da Lyung; Hong, Sung Yu; Lee, Sang Hak; Kang, Seok Min; Choi, Dong Hoon; Jang, Yangsoo; Kim, Se Hoon; Park, Sungha.

In: Circulation Journal, Vol. 78, No. 5, 2014, p. 1197-1205.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Blocking the receptor for advanced glycation end product activation attenuates autoimmune myocarditis

AU - Yang, Woo In

AU - Lee, Dajeong

AU - Lee, Da Lyung

AU - Hong, Sung Yu

AU - Lee, Sang Hak

AU - Kang, Seok Min

AU - Choi, Dong Hoon

AU - Jang, Yangsoo

AU - Kim, Se Hoon

AU - Park, Sungha

PY - 2014

Y1 - 2014

N2 - 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.

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VL - 78

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