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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 
 International Journal of Cardiology, Vol.252 : 156-162, 2018 
Journal Title
 International Journal of Cardiology 
Issue Date
Ethyl pyruvate ; HMGB1 protein ; Hyperglycemia ; Myocardial reperfusion injury
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 (50mg/kg) upon reperfusion, HG-Sham, HG-I/R-C, and HG-I/R-EP treatment upon reperfusion. HG was induced by 1.2g/kg dextrose. I/R was induced by ligation of the left anterior descending artery for 30min followed by 4h 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-kappaB pathway compared to NG following I/R, which all could be attenuated by EP. EP treatment was associated with diminished tumor necrosis factor-alpha, interleukin-1beta, 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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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
곽영란(Kwak, Young Lan) ORCID logo https://orcid.org/0000-0002-2984-9927
소사라(Soh, Sa Rah) ORCID logo https://orcid.org/0000-0001-5022-4617
송종욱(Song, Jong Wook) ORCID logo https://orcid.org/0000-0001-7518-2070
심재광(Shim, Jae Kwang) ORCID logo https://orcid.org/0000-0001-9093-9692
전지혜(Jun, Ji Hae) ORCID logo https://orcid.org/0000-0002-8080-0715
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