Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate

High-mobility group box-1 (HMGB1) acts as a proinflammatory cytokine that triggers and amplifies the inflammation cascade following ischemia/reperfusion (I/R). Ethyl pyruvate (EP) has been reported to inhibit HMGB1 release in several I/R models. This study was designed to investigate the potential r...

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Main Authors:	LIN, YUNLING, CHEN, LIANGLONG, LI, WEIWEI, FANG, JUN
Format:	Online
Language:	English
Published:	D.A. Spandidos 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353799/

id	pubmed-4353799
recordtype	oai_dc
spelling	pubmed-43537992015-03-16 Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate LIN, YUNLING CHEN, LIANGLONG LI, WEIWEI FANG, JUN Articles High-mobility group box-1 (HMGB1) acts as a proinflammatory cytokine that triggers and amplifies the inflammation cascade following ischemia/reperfusion (I/R). Ethyl pyruvate (EP) has been reported to inhibit HMGB1 release in several I/R models. This study was designed to investigate the potential role of HMGB1 in a rat myocardial I/R model and to determine the effect of EP. Male Sprague Dawley rats were subjected to 30 min myocardial ischemia and 48 h reperfusion. In protocol 1, the rats were assigned to one of four groups (n=16 per group): Phosphate-buffered saline (PBS) or recombinant human HMGB1 (rhHMGB1) at three different doses (1, 10 or 100 μg/kg). In protocol 2, the rats were also assigned to one of four groups (n=16 per group): Sham, control, EP and EP + rhHMGB1. EP (40 mg/kg) or rhHMGB1 (100 μg/kg) was injected intravenously prior to reperfusion. Hemodynamic measurements were performed, and myocardial infarct size (IS) was calculated. Western blotting was conducted to evaluate HMGB1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. In the protocol 1 rats, the IS was markedly increased in the rhHMGB1 (100 μg/kg) group compared with that in the PBS group, and this increase was accompanied by elevated levels of TNF-α and IL-6. In the protocol 2 rats, I/R resulted a 4.8-fold increase in HMGB1 expression with an increased IS and impaired cardiac function compared with the sham group. EP significantly inhibited the elevated HMGB1 level, suppressed the activated TNF-α and IL-6 and reduced cardiac dysfunction. This cardioprotection was abolished by rhHMGB1. In conclusion, accumulation of HMGB1 is deleterious to the heart following myocardial I/R. EP can exert a strong protective effect against myocardial I/R injury, and these benefits are associated with a reduction in HMGB1. D.A. Spandidos 2015-04 2015-02-13 /pmc/articles/PMC4353799/ /pubmed/25780465 http://dx.doi.org/10.3892/etm.2015.2290 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	LIN, YUNLING CHEN, LIANGLONG LI, WEIWEI FANG, JUN
spellingShingle	LIN, YUNLING CHEN, LIANGLONG LI, WEIWEI FANG, JUN Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate
author_facet	LIN, YUNLING CHEN, LIANGLONG LI, WEIWEI FANG, JUN
author_sort	LIN, YUNLING
title	Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate
title_short	Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate
title_full	Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate
title_fullStr	Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate
title_full_unstemmed	Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate
title_sort	role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate
description	High-mobility group box-1 (HMGB1) acts as a proinflammatory cytokine that triggers and amplifies the inflammation cascade following ischemia/reperfusion (I/R). Ethyl pyruvate (EP) has been reported to inhibit HMGB1 release in several I/R models. This study was designed to investigate the potential role of HMGB1 in a rat myocardial I/R model and to determine the effect of EP. Male Sprague Dawley rats were subjected to 30 min myocardial ischemia and 48 h reperfusion. In protocol 1, the rats were assigned to one of four groups (n=16 per group): Phosphate-buffered saline (PBS) or recombinant human HMGB1 (rhHMGB1) at three different doses (1, 10 or 100 μg/kg). In protocol 2, the rats were also assigned to one of four groups (n=16 per group): Sham, control, EP and EP + rhHMGB1. EP (40 mg/kg) or rhHMGB1 (100 μg/kg) was injected intravenously prior to reperfusion. Hemodynamic measurements were performed, and myocardial infarct size (IS) was calculated. Western blotting was conducted to evaluate HMGB1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. In the protocol 1 rats, the IS was markedly increased in the rhHMGB1 (100 μg/kg) group compared with that in the PBS group, and this increase was accompanied by elevated levels of TNF-α and IL-6. In the protocol 2 rats, I/R resulted a 4.8-fold increase in HMGB1 expression with an increased IS and impaired cardiac function compared with the sham group. EP significantly inhibited the elevated HMGB1 level, suppressed the activated TNF-α and IL-6 and reduced cardiac dysfunction. This cardioprotection was abolished by rhHMGB1. In conclusion, accumulation of HMGB1 is deleterious to the heart following myocardial I/R. EP can exert a strong protective effect against myocardial I/R injury, and these benefits are associated with a reduction in HMGB1.
publisher	D.A. Spandidos
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353799/
_version_	1613196668022292480

Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate

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