Inhibition of PKCβ2 overexpression ameliorates myocardial ischaemia/reperfusion injury in diabetic rats via restoring caveolin-3/Akt signaling

2015 ◽  
Vol 129 (4) ◽  
pp. 331-344 ◽  
Author(s):  
Yanan Liu ◽  
Jiqin Jin ◽  
Shigang Qiao ◽  
Shaoqing Lei ◽  
Songyan Liao ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Myocardial Ischaemia ◽  
Akt Signaling ◽  
Diabetic Rats ◽  
Cardiomyocyte Apoptosis ◽  
Ischaemia Reperfusion Injury ◽  
Mitochondrial Injury ◽  
Ischaemia Reperfusion

We demonstrate that ruboxistaurin protects against diabetes-associated myocardial I/R injury primarily by restoring caveolin-3/Akt signalling. Interestingly, caveolin-3 and Akt, important salvage molecules regulated by PKCβ2, mediate post-ischaemic cardioprotection in diabetes by attenuation of cardiomyocyte apoptosis and mitochondrial injury.

Role of microRNA-195 in cardiomyocyte apoptosis induced by myocardial ischaemia–reperfusion injury

2016 ◽  
Vol 95 (1) ◽  
pp. 99-108 ◽  
Author(s):  
CHANG-KUI GAO ◽  
HUI LIU ◽  
CHENG-JI CUI ◽  
ZHAO-GUANG LIANG ◽  
HONG YAO ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Myocardial Ischaemia ◽  
Cardiomyocyte Apoptosis ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion

scholarly journals Roles of HDAC3-orchestrated circadian clock gene oscillations in diabetic rats following myocardial ischaemia/reperfusion injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhen Qiu ◽  
Hao Ming ◽  
Shaoqing Lei ◽  
Bin Zhou ◽  
Bo Zhao ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Reperfusion Injury ◽  
Myocardial Ischaemia ◽  
High Glucose ◽  
Clock Genes ◽  
Diabetic Rats ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
The Stability

AbstractThe circadian clock is closely related to the development of diabetes mellitus and cardiovascular disease, and disruption of the circadian clock exacerbates myocardial ischaemia/reperfusion injury (MI/RI). HDAC3 is a key component of the circadian negative feedback loop that controls the expression pattern of the circadian nuclear receptor Rev-erbα to maintain the stability of circadian genes such as BMAL1. However, the mechanism by which the HDAC3-orchestrated Rev-erbα/BMAL1 pathway increases MI/RI in diabetes and its relationship with mitophagy have yet to be elucidated. Here, we observed that the clock genes Rev-erbα, BMAL1, and C/EBPβ oscillations were altered in the hearts of rats with streptozotocin (STZ)-induced diabetes, with upregulated HDAC3 expression. Oscillations of Rev-erbα and BMAL1 were rapidly attenuated in diabetic MI/R hearts versus non-diabetic I/RI hearts, in accordance with impaired and rhythm-disordered circadian-dependent mitophagy that increased injury. Genetic knockdown of HDAC3 significantly attenuated diabetic MI/RI by mediating the Rev-erbα/BMAL1 circadian pathway to recover mitophagy. Primary cardiomyocytes with or without HDAC3 siRNA and Rev-erbα siRNA were exposed to hypoxia/reoxygenation (H/R) in vitro. The expression of HDAC3 and Rev-erbα in cardiomyocytes was increased under high-glucose conditions compared with low-glucose conditions, with decreased BMAL1 expression and mitophagy levels. After H/R stimulation, high glucose aggravated H/R injury, with upregulated HDAC3 and Rev-erbα expression and decreased BMAL1 and mitophagy levels. HDAC3 and Rev-erbα siRNA can alleviate high glucose-induced and H/R-induced injury by upregulating BMAL1 to increase mitophagy. Collectively, these findings suggest that disruption of HDAC3-mediated circadian gene expression oscillations induces mitophagy dysfunction, aggravating diabetic MI/RI. Cardiac-specific HDAC3 knockdown could alleviate diabetic MI/RI by regulating the Rev-erbα/BMAL1 pathway to restore the activation of mitophagy.

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