scholarly journals Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial Ischemia/Reperfusion Injury via Mitochondria Apoptosis Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Yang Wu ◽  
Yan Leng ◽  
Qingtao Meng ◽  
Rui Xue ◽  
Bo Zhao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Ischemia ◽  
Histone Deacetylases ◽  
Mitochondrial Permeability Transition ◽  
Apoptotic Cell ◽  
Trichostatin A ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Apoptosis Pathway ◽  
Myocardial Ischemia Reperfusion

Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion. H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R). Results. Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity. MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA). TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP), and decreased cell apoptosis. Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro. Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression. Conclusions. Both diabetes mellitus and MI/R injury increased cardiac HDACs activity. Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim.

scholarly journals Remote liver ischemic preconditioning attenuates myocardial ischemia/reperfusion injury in streptozotocin-induced diabetic rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinhao Liu ◽  
Hui Chen ◽  
Zhibing Yan ◽  
Lei Du ◽  
Dou Huang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Myocardial Ischemia Reperfusion ◽  
Gsk 3Β

AbstractDiabetes mellitus (DM) exhibits a higher sensitivity to myocardial ischemia/reperfusion (I/R) injury and may compromise the effectiveness of cardioprotective interventions, including ischemic preconditioning. We previously found that liver ischemic preconditioning (RLIPC) could limit infarct size post I/R in non-diabetic rat hearts and further exerted anti-arrhythmic effects in diabetic or non-diabetic rats after myocardial I/R, however, little is known regarding the effect of RLIPC on infarct-sparing in diabetic hearts. In this study, we evaluated the protective effects of RLIPC on I/R injury in streptozotocin-induced type 1 diabetic rats. Type 1 diabetes mellitus was induced by one-time intraperitoneal injection of streptozotocin in Sprague–Dawley rats. Rats were exposed to 45 min of left anterior descend in (LAD) coronary artery occlusion, followed by 3 h of reperfusion. For liver ischemic preconditioning, four cycles of 5 min of liver I/R stimuli were performed before LAD occlusion. The cardioprotective effect of RLIPC was determined in diabetic rats. Compared to non-RLIPC treated DM rats, RLIPC treatment significantly reduced infarct size and cardiac tissue damage, inhibited apoptosis in diabetic hearts post I/R. RLIPC also improved cardiac functions including LVESP, LVEDP, dp/dtmax, and − dp/dtmax. In addition, RLIPC preserved cardiac morphology by reducing the pathological score post I/R in diabetic hearts. Finally, Westernblotting showed that RLIPC stimulated phosphorylation of ventricular GSK-3β and STAT-5, which are key components of RISK and SAFE signaling pathways. Our study showed that liver ischemic preconditioning retains strong cardioprotective properties in diabetic hearts against myocardial I/R injury via GSK-3β/STAT5 signaling pathway.

scholarly journals Remote Liver Ischemic Preconditioning Attenuates Myocardial Ischemia/reperfusion Injury in Streptozotocin-induced Diabetic Rats

2020 ◽  
Author(s):  
Xinhao Liu ◽  
Hui Chen ◽  
Zhibing Yan ◽  
Lei Du ◽  
Dou Huang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion

Abstract BACKGROUND: Diabetes mellitus (DM) exhibits a higher sensitivity to myocardial ischemia/reperfusion(I/R)injury and may compromise the effectiveness of cardioprotective interventions, including ischemic preconditioning. We previously found that liver ischemic preconditioning(RLIPC) could limit infarct size post I/R in normal rat hearts and further exerted anti-arrhythmic effects in diabetic or non-diabetic rats after myocardial I/R, however, little is known regarding the effect of RLIPC on infarct-sparing in diabetic hearts. In this study, we evaluated the protective effects of RLIPC on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats.METHODS:Type 1 diabetes mellitus was induced by one-time intraperitoneal injection of streptozotocin in Sprague–Dawley rats. Rats were exposed to 45 min of left anterior descendin(LAD) coronary artery occlusion, followed by 3 h of reperfusion. For liver ischemic preconditioning, four cycles of 5 min of liver I/R stimuli were performed before LAD occlusion. the cardioprotective effect of RLIPC was determined in diabetic rats.RESULTS: Compared to non-RLIPC treated DM rats, RLIPC treatment significantly reduced infarct size in diabetic hearts post I/R. RLIPC also improved cardiac functions including LVESP, LVEDP, dp/dtmax, and -dp/dtmax. In addition, RLIPC could largely preserved cardiac morphology by reducing the pathological score post I/R in diabetic hearts. Finally, western blotting analysis showed that RLIPC stimulated phosphorylation of ventricular GSK-3β and STAT-5, which are key components of RISK and SAFE signaling pathways.

Expression profiles of long noncoding RNAs in type 2 diabetes mellitus rat associated with the progression of ischemia-reperfursion injury

2020 ◽  
Author(s):  
Wenhao Song ◽  
Yao Gong ◽  
Pei Tu ◽  
Lin Zhang ◽  
Zhili Jin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Expression Profiles ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Myocardial Ischemia Reperfusion

Abstract Background The aim of this study was to analyze the expressions of long noncoding RNA(lncRNA) in rat with type 2 diabetes mellitus(T2DM) complicated with acute myocardial ischemia reperfusion injury(IRI). Methods Type 2 diabetic rats were induced by high calorie diet combined with streptozotocin. IRI rats models were established by the ligation and release of left anterior descending coronary artery(LAD). The expression levels of lncRNA and mRNA in myocardial tissues of rats were detected via high-throughput sequencing technology, and Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Result Transcriptome analyses were performed to show expression profiles of mRNAs and lncRNAs in myocardial tissues of diabetic rats with IRI. A total of 2,476 lncRNAs and 710 mRNAs were differentially expressed between operation group and sham operation group. Then, an mRNA-lncRNA coexpression network was constructed. Finally, the present study verified that TCONS_00036439、TCONS_00151548、TCONS_00153276、TCONS_00344188、TCONS_00277692、TCONS_00236469、TCONS_00236468、TCONS_00153290、TCONS_00360941、TCONS_00142622 were associated with the initiation and development of ischemia reperfusion injury. Then, an lncRNA-mRNA coexpression network was constructed. Conclusion There is differential expression of lncRNAs in myocardial IRI tissues of diabetic rats. Building gene regulation networks to find the nodal gene and lncRNA is useful for understanding the pathogenesis of type 2 diabetes mellitus complicated with acute myocardial ischemia reperfusion injury and providing new therapy target.

scholarly journals N-Acetylcysteine Restores Sevoflurane Postconditioning Cardioprotection against Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Jiefu Lin ◽  
Tingting Wang ◽  
Yalan Li ◽  
Mengxia Wang ◽  
Haobo Li ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Cd36 Expression ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Sevoflurane Postconditioning

The effect of sevoflurane postconditioning (sevo-postC) cardioprotection is compromised in diabetes which is associated with increased oxidative stress. We hypothesized that antioxidant N-Acetylcysteine may enhance or restore sevo-postC cardioprotection in diabetes. Control or streptozotocin-induced Type 1 diabetic rats were either untreated or treated with N-Acetylcysteine for four weeks starting at five weeks after streptozotocin injection and were subjected to myocardial ischemia-reperfusion injury (IRI), in the absence or presence of sevo-postC. Diabetes showed reduction of cardiac STAT3 activation (p-STAT3) and adiponectin with concomitantly increase of FoxO1 and CD36, which associated with reduced sevo-postC cardioprotection. N-Acetylcysteine and sevo-postC synergistically reduced the infarct size in diabetic groups. N-Acetylcysteine remarkably increased cardiac p-STAT3 which was further enhanced by sevo-postC. N-Acetylcysteine but not sevo-postC decreased myocardial FoxO1 while sevo-postC but not N-Acetylcysteine significantly increased myocardiac adiponectin in diabetic rats. It is concluded that late stage diabetic rats displayed reduction of cardiac p-STAT3, adiponectin deficiency, and increase of FoxO1 and CD36 expression, which may be responsible for the loss of myocardial responsiveness to sevo-postC cardioprotection. N-Acetylcysteine restored Sevo-postC cardioprotection in diabetes possibly through enhancing cardiac p-STAT3 and adiponectin and reducing Fox1 and CD36.

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