1. Inhibition of HMGB1 alleviates myocardial ischemia/reperfusion injury in diabetic mice via suppressing autophagy.
- Author
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Chen, Chuanbin, Lu, Chuanghong, He, Dewei, Na, Na, Wu, Yunjiao, Luo, Zuchun, and Huang, Feng
- Subjects
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MYOCARDIAL ischemia , *HIGH mobility group proteins , *REPERFUSION injury , *AUTOPHAGY - Abstract
Diabetes aggravates myocardial ischemia/reperfusion (I/R) injury (MI/RI). The association between high mobility group box 1 protein (HMGB1) and autophagy in diabetic MI/RI remains unknown. Therefore, we investigated whether inhibiting HMGB1 can regulate autophagy in diabetic mice (DM) after I/R injury. I/R models of C57BL/KsJ mice and db/db mice were established. Histological changes, infarct size (IS), HMGB1 protein, and autophagy-related proteins were detected after 24h of reperfusion. In DM treatment groups, anti-HMGB1 antibody (H-Ig) was injected via tail vein after reperfusion for 15min, and the above-mentioned experimental methods were performed at the end of reperfusion. Compared with the I/R group, the pathological myocardial damage and IS were significantly increased in the I/R (DM) group. Additionally, the levels of HMGB1, Beclin1, and LC3II/LC3I ratio were remarkably higher in the I/R (DM) group than those in the I/R group, while p62 level was lower. In the H-Ig (DM) group, injection of H-Ig significantly reduced the IS, as well as alleviated pathological myocardial damage. Moreover, Beclin1, LC3II/LC3I ratio, and p62 levels were notably reversed after this treatment. I/R-induced myocardium was aggravated by diabetes, which may be related to increased release of HMGB1 and activated autophagy. Inhibition of HMGB1 alleviates diabetic MIRI which was associated with reduced autophagy. • The first study showing the relationship between HMGB1 and over-activated autophagy in diabetic MIRI • The study observes reperfusion up to 24 h, ensuring that the effectiveness of inhibition of HMGB1 is retained. • The treatment node is selected after reperfusion, which is a feasible scheme for clinical needs. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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