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High glucose protects cardiomyocytes against ischaemia/reperfusion injury by suppressing myocardiocyte apoptosis via circHIPK3/miR-29b/AKT3 signalling |
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| Authors: | Nan Cheng Chang Jin Ping Jin Dan Zhu Zuoxu Hou |
| Affiliation: | 1. Department of Cardiovascular Surgery, Chinese PLA General Hospital, Beijing, China Contribution: Conceptualization (equal), Formal analysis (equal), Investigation (equal), Writing - original draft (equal), Writing - review & editing (equal);2. Medical Innovation Research Division, Research Center for Biomedical Engineering, Chinese PLA General Hospital, Beijing, China Contribution: Investigation (equal), Methodology (equal), Resources (equal);3. Department of Cardiovascular Surgery, The First Affiliated Hospital of Air Force Military Medical University, Xi'an, China Contribution: Formal analysis (equal), Investigation (equal), Visualization (equal);4. Department of Arrhythmia, Qinghai Cardio-Cerebrovascular Hospital, Xi'ning, China Contribution: Investigation (equal), Resources (equal), Validation (equal);5. Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People's Liberation Army, Wuhan, China |
| Abstract: | High glucose promoted expression of AKT3, a direct target gene of miR-29b, by regulating circHIPK3 that functioned as ceRNA to sponge and down-regulate miR-29b. As a potential target gene of miR-29b, AKT3 plays a crucial role in the pathogenesis of myocardial ischaemia/reperfusion (I/R) injury, and this study aimed to investigate the potential role of high glucose in the outcome of I/R injury. qPCR and luciferase assay were carried out to investigate the relationship between the expression of circHIPK3, miR-29b and ATK3 mRNA. Immunohistochemistry and TUNEL were performed to analyse the relationship between AKT3 expression and apoptosis of myocardiocytes in vivo. No obvious difference in myocardial functions was observed between I/R and control rats under hyperglycaemia (HG) and normal glucose (NG) conditions, except that the infarct size/area at risk (IS/AR) ratio and the amount of h-FABP expression were different under HG and NG conditions. The expression of circHIPK3 and ATK3 was significantly elevated in the rats preconditioned by NG, whereas the expression of miR-29a was remarkably decreased. Meanwhile, the apoptosis of myocardial tissue was reduced in the rats preconditioned by NG. Luciferase assay confirmed that miR-29a played a repressive role in the expression of circHIPK3 and ATK3. And subsequent study indicated that the over-expressed AKT3 could rescue the increased cell apoptosis rate induced by the knockdown of circHIPK3. In this study, we demonstrated that high glucose protects cardiomyocytes against I/R associated injury by suppressing apoptosis and high glucose promoted the expression of AKT3 by regulating the expression of circHIPK3/miR-29b. |
| Keywords: | AKT3 apoptosis circHIPK3 high glucose ischaemia/reperfusion miR-29b |