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 language | English |
|---|---|
| Pages (from-to) | 156-162 |
| Number of pages | 7 |
| Journal | International Journal of Cardiology |
| Volume | 252 |
| DOIs | |
| Publication status | Published - 2018 Feb 1 |
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All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
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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 journal › Article
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.
UR - http://www.scopus.com/inward/record.url?scp=85034612955&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034612955&partnerID=8YFLogxK
U2 - 10.1016/j.ijcard.2017.11.038
DO - 10.1016/j.ijcard.2017.11.038
M3 - Article
C2 - 29169909
AN - SCOPUS:85034612955
VL - 252
SP - 156
EP - 162
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
ER -