Ethyl pyruvate attenuates myocardial ischemia-reperfusion injury exacerbated by hyperglycemia via retained inhibitory effect on HMGB1

Sarah Soh, Ji Hae Jun, Jong Wook Song, Eun Jung Shin, Young Lan Kwak, Jae Kwang Shim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background Hyperglycemia (HG) exacerbates myocardial ischemia/reperfusion (I/R) injury and renders protective strategies ineffective by amplified inflammatory response via enhanced high-mobility group box-1 (HMGB1) release. This study investigated the role of ethyl pyruvate (EP) against myocardial I/R injury under a clinically relevant HG condition. Methods Sprague-Dawley rats (n = 76) were randomly assigned to 6 groups: normoglycemia (NG)-Sham, NG-I/R-control (C, saline), NG-I/R-EP treatment (50 mg/kg) upon reperfusion, HG-Sham, HG-I/R-C, and HG-I/R-EP treatment upon reperfusion. HG was induced by 1.2 g/kg dextrose. I/R was induced by ligation of the left anterior descending artery for 30 min followed by 4 h of reperfusion. Results HG resulted in exacerbation of myocardial infarct size by 19% with amplified activation of HMGB1–receptors of advanced glycation end products/toll like receptors–NF-κB pathway compared to NG following I/R, which all could be attenuated by EP. EP treatment was associated with diminished tumor necrosis factor-α interleukin-1β and interleukin-6 expressions. It also served to normalize the increase in pro-apoptotic Bax and the decrease in anti-apoptotic Bcl-2 protein levels. These effects were associated with decreased myocardial apoptosis and infarct size (by 30% and 36% in the NG and HG groups, respectively) regardless of the glycemic condition. Conclusion HG exacerbated myocardial I/R injury through amplified inflammatory response via increased HMGB1 level. EP treatment upon reperfusion conveyed significant myocardial protection against the I/R injury under both NG and HG conditions. Common to both glycemic conditions, associated mechanisms involved attenuated increase in HMGB1 level and suppression of its down-stream pathways.

Original languageEnglish
Pages (from-to)156-162
Number of pages7
JournalInternational Journal of Cardiology
Volume252
DOIs
Publication statusPublished - 2018 Feb 1

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Myocardial Reperfusion Injury
Reperfusion Injury
Hyperglycemia
Reperfusion
Myocardial Ischemia
Ischemia
Myocardial Infarction
ethyl pyruvate
Advanced Glycosylation End Products
Interleukin-1
Ligation
Sprague Dawley Rats
Interleukin-6
Arteries
Tumor Necrosis Factor-alpha
Apoptosis

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

@article{c6e91614aa94432c937355cf2e8454fe,
title = "Ethyl pyruvate attenuates myocardial ischemia-reperfusion injury exacerbated by hyperglycemia via retained inhibitory effect on HMGB1",
abstract = "Background Hyperglycemia (HG) exacerbates myocardial ischemia/reperfusion (I/R) injury and renders protective strategies ineffective by amplified inflammatory response via enhanced high-mobility group box-1 (HMGB1) release. This study investigated the role of ethyl pyruvate (EP) against myocardial I/R injury under a clinically relevant HG condition. Methods Sprague-Dawley rats (n = 76) were randomly assigned to 6 groups: normoglycemia (NG)-Sham, NG-I/R-control (C, saline), NG-I/R-EP treatment (50 mg/kg) upon reperfusion, HG-Sham, HG-I/R-C, and HG-I/R-EP treatment upon reperfusion. HG was induced by 1.2 g/kg dextrose. I/R was induced by ligation of the left anterior descending artery for 30 min followed by 4 h of reperfusion. Results HG resulted in exacerbation of myocardial infarct size by 19{\%} with amplified activation of HMGB1–receptors of advanced glycation end products/toll like receptors–NF-κB pathway compared to NG following I/R, which all could be attenuated by EP. EP treatment was associated with diminished tumor necrosis factor-α interleukin-1β and interleukin-6 expressions. It also served to normalize the increase in pro-apoptotic Bax and the decrease in anti-apoptotic Bcl-2 protein levels. These effects were associated with decreased myocardial apoptosis and infarct size (by 30{\%} and 36{\%} in the NG and HG groups, respectively) regardless of the glycemic condition. Conclusion HG exacerbated myocardial I/R injury through amplified inflammatory response via increased HMGB1 level. EP treatment upon reperfusion conveyed significant myocardial protection against the I/R injury under both NG and HG conditions. Common to both glycemic conditions, associated mechanisms involved attenuated increase in HMGB1 level and suppression of its down-stream pathways.",
author = "Sarah Soh and Jun, {Ji Hae} and Song, {Jong Wook} and Shin, {Eun Jung} and Kwak, {Young Lan} and Shim, {Jae Kwang}",
year = "2018",
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doi = "10.1016/j.ijcard.2017.11.038",
language = "English",
volume = "252",
pages = "156--162",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",

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Ethyl pyruvate attenuates myocardial ischemia-reperfusion injury exacerbated by hyperglycemia via retained inhibitory effect on HMGB1. / Soh, Sarah; Jun, Ji Hae; Song, Jong Wook; Shin, Eun Jung; Kwak, Young Lan; Shim, Jae Kwang.

In: International Journal of Cardiology, Vol. 252, 01.02.2018, p. 156-162.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ethyl pyruvate attenuates myocardial ischemia-reperfusion injury exacerbated by hyperglycemia via retained inhibitory effect on HMGB1

AU - Soh, Sarah

AU - Jun, Ji Hae

AU - Song, Jong Wook

AU - Shin, Eun Jung

AU - Kwak, Young Lan

AU - Shim, Jae Kwang

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Background Hyperglycemia (HG) exacerbates myocardial ischemia/reperfusion (I/R) injury and renders protective strategies ineffective by amplified inflammatory response via enhanced high-mobility group box-1 (HMGB1) release. This study investigated the role of ethyl pyruvate (EP) against myocardial I/R injury under a clinically relevant HG condition. Methods Sprague-Dawley rats (n = 76) were randomly assigned to 6 groups: normoglycemia (NG)-Sham, NG-I/R-control (C, saline), NG-I/R-EP treatment (50 mg/kg) upon reperfusion, HG-Sham, HG-I/R-C, and HG-I/R-EP treatment upon reperfusion. HG was induced by 1.2 g/kg dextrose. I/R was induced by ligation of the left anterior descending artery for 30 min followed by 4 h of reperfusion. Results HG resulted in exacerbation of myocardial infarct size by 19% with amplified activation of HMGB1–receptors of advanced glycation end products/toll like receptors–NF-κB pathway compared to NG following I/R, which all could be attenuated by EP. EP treatment was associated with diminished tumor necrosis factor-α interleukin-1β and interleukin-6 expressions. It also served to normalize the increase in pro-apoptotic Bax and the decrease in anti-apoptotic Bcl-2 protein levels. These effects were associated with decreased myocardial apoptosis and infarct size (by 30% and 36% in the NG and HG groups, respectively) regardless of the glycemic condition. Conclusion HG exacerbated myocardial I/R injury through amplified inflammatory response via increased HMGB1 level. EP treatment upon reperfusion conveyed significant myocardial protection against the I/R injury under both NG and HG conditions. Common to both glycemic conditions, associated mechanisms involved attenuated increase in HMGB1 level and suppression of its down-stream pathways.

AB - Background Hyperglycemia (HG) exacerbates myocardial ischemia/reperfusion (I/R) injury and renders protective strategies ineffective by amplified inflammatory response via enhanced high-mobility group box-1 (HMGB1) release. This study investigated the role of ethyl pyruvate (EP) against myocardial I/R injury under a clinically relevant HG condition. Methods Sprague-Dawley rats (n = 76) were randomly assigned to 6 groups: normoglycemia (NG)-Sham, NG-I/R-control (C, saline), NG-I/R-EP treatment (50 mg/kg) upon reperfusion, HG-Sham, HG-I/R-C, and HG-I/R-EP treatment upon reperfusion. HG was induced by 1.2 g/kg dextrose. I/R was induced by ligation of the left anterior descending artery for 30 min followed by 4 h of reperfusion. Results HG resulted in exacerbation of myocardial infarct size by 19% with amplified activation of HMGB1–receptors of advanced glycation end products/toll like receptors–NF-κB pathway compared to NG following I/R, which all could be attenuated by EP. EP treatment was associated with diminished tumor necrosis factor-α interleukin-1β and interleukin-6 expressions. It also served to normalize the increase in pro-apoptotic Bax and the decrease in anti-apoptotic Bcl-2 protein levels. These effects were associated with decreased myocardial apoptosis and infarct size (by 30% and 36% in the NG and HG groups, respectively) regardless of the glycemic condition. Conclusion HG exacerbated myocardial I/R injury through amplified inflammatory response via increased HMGB1 level. EP treatment upon reperfusion conveyed significant myocardial protection against the I/R injury under both NG and HG conditions. Common to both glycemic conditions, associated mechanisms involved attenuated increase in HMGB1 level and suppression of its down-stream pathways.

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