The HMGB1-TLR4 axis contributes to myocardial ischemia/reperfusion injury via regulation of cardiomyocyte apoptosis

Toll-like receptor 4 (TLR4) and its ligand high mobility group box 1 (HMGB1), are known for playing central roles in ischemia-reperfusion injury in myocardium. However, the detailed mechanisms of TLR4 and HMGB1 are not fully understood. The aim of this study was to investigate the effects and possib...

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Bibliographic Details
Published in:Gene 2013-09, Vol.527 (1), p.389-393
Main Authors: Ding, Hua-Sheng, Yang, Jun, Chen, Ping, Yang, Jian, Bo, Sun-Qing, Ding, Jia-Wang, Yu, Qin-Qin
Format: Article
Language:English
Subjects:
Animals
Apoptosis
bcl-2-Associated X Protein - metabolism
Gene Expression
HMGB1 Protein - metabolism
Male
Mice
Mice, Inbred C3H
Myocardial Reperfusion Injury - metabolism
Myocardial Reperfusion Injury - pathology
Myocytes, Cardiac - physiology
Proto-Oncogene Proteins c-bcl-2 - metabolism
Toll-Like Receptor 4 - metabolism
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
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Summary:Toll-like receptor 4 (TLR4) and its ligand high mobility group box 1 (HMGB1), are known for playing central roles in ischemia-reperfusion injury in myocardium. However, the detailed mechanisms of TLR4 and HMGB1 are not fully understood. The aim of this study was to investigate the effects and possible mechanisms of the HMGB1-TLR4 axis and cardiomyocyte apoptosis on myocardial ischemic damage. Artificial oxygen ventilated anesthetized C3H/HeN mice and C3H/HeJ mice were subjected to 30 min of left anterior descending coronary artery occlusion followed by 6h of reperfusion. The myocardial infarct size, HMGB1 levels, apoptosis index, Bax, Bcl-2 and TNF-α mRNA levels were assessed. The results showed that a lowered amount of cardiomyocyte apoptosis and infarct size in the myocardium of TLR4-mutant mice after myocardial I/R and that TLR4 deficiency notably inhibited the expression of HMGB1 and TNF-a, both of which were up-regulated by ischemia/reperfusion. These findings suggest that the HMGB1-TLR4 axis plays a pathogenic role in triggering cardiomyocyte apoptosis during myocardial I/R injury and that the possible mechanism for this process is the result of released cytokines and inflammatory response involved in the HMGB1/TLR4-related pathway.
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2013.05.041