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.

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.

Abstract 1000: Dichotomous Roles Of TNF-α Receptors p55 And p75 In Acute Ischemia/reperfusion Injury And Late Ischemic Preconditioning

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Michael P Flaherty ◽  
Yiru Guo ◽  
Xian-Liang Tang ◽  
Sumit Tiwari ◽  
Greg Hunt ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemic Preconditioning ◽  
Coronary Occlusion ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Acute Myocardial Ischemia ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

We have previously demonstrated that TNF-alpha signaling is critical for the development of protection afforded by the late phase of ischemic preconditioning (PC). In the current study, we investigated the roles of p55 (TNFR-I) and p75 (TNFR-II) in acute myocardial ischemia/reperfusion injury as well as late PC. Wild-type (WT, B6 and B6,129 strains), TNF-a−/−, p55−/−, p75−/−, and p55−/−/p75−/− double-knockout mice underwent a 30-min coronary occlusion followed by 4 h of reperfusion with or without six cycles of coronary occlusion/reperfusion (O/R) 24 h earlier. Six cycles of O/R reduced infarct size 24 h later in B6 as well as B6,129 WT mice, indicating a rob ust late PC effect (Figure ). This infarct-sparing effect of late PC was abolished in the absence of TNF-a, p55, p75, and both p55/p75, indicating that TNF-a signaling is critical for the development of late PC protection; and that signaling via both p55 and p75 is necessary for the development of protection. In nonpreconditioned TNF-a−/− and p75−/− mice, infarct size was similar to that observed in strain-matched WT mice (Figure ). However, infarct size in nonpreconditioned p55−/− mice was reduced compared with nonpreconditioned WT mice (46.8 ± 2.8% vs. 63.4 ± 3.2%, P < 0.05, Figure ). These observations were confirmed via linear regression analysis of myocardial risk region and infarct size. We conclude that nonredundant TNF-a signaling via both p55 and p75 is crucial for the development of late PC protection. However, the reduction in infarct size in naïve p55−/− mice indicates a deleterious role of this receptor during acute myocardial ischemia/reperfusion injury.

scholarly journals Hyperglycemia-Induced Inhibition of DJ-1 Expression Compromised the Effectiveness of Ischemic Postconditioning Cardioprotection in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Min Liu ◽  
Bin Zhou ◽  
Zhong-Yuan Xia ◽  
Bo Zhao ◽  
Shao-Qing Lei ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Ischemia And Reperfusion Injury ◽  
Correlation Relationship ◽  
Myocardial Ischemia Reperfusion

Ischemia postconditioning (IpostC) is an effective way to alleviate ischemia and reperfusion injury; however, the protective effects seem to be impaired in candidates with diabetes mellitus. To gain deep insight into this phenomenon, we explored the role of DJ-1, a novel oncogene, that may exhibit powerful antioxidant capacity in postconditioning cardioprotection in a rat model of myocardial ischemia reperfusion injury. Compared with normal group, cardiac DJ-1 was downregulated in diabetes. Larger postischemic infarct size as well as exaggeration of oxidative stress was observed, while IpostC reversed the above changes in normal but not in diabetic rats. DJ-1 was increased after ischemia and postconditioning contributed to a further elevation; however, no alteration of DJ-1 was documented in all subgroups of diabetic rats. Alteration of the cardioprotective PI3K/Akt signaling proteins may be responsible for the ineffectiveness of postconditioning in diabetes. There is a positive correlation relationship between p-Akt and DJ-1 but a negative correlation between infarct size and DJ-1, which may partially explain the interaction of DJ-1 and IpostC cardioprotection. Our result indicates a beneficial role of DJ-1 in myocardial ischemia reperfusion. Downregulation of cardiac DJ-1 may be responsible for the compromised diabetic heart responsiveness to IpostC cardioprotection.

scholarly journals Dynamic alteration of adiponectin/adiponectin receptor expression and its impact on myocardial ischemia/reperfusion in type 1 diabetic mice

2011 ◽  
Vol 301 (3) ◽  
pp. E447-E455 ◽  
Author(s):  
Yanzhuo Ma ◽  
Yi Liu ◽  
Shaowei Liu ◽  
Yan Qu ◽  
Rutao Wang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Dynamic Change ◽  
Receptor Expression ◽  
Diabetic Patients ◽  
Dependent Manner ◽  
Myocardial Ischemia Reperfusion ◽  
Underlying Mechanisms

The present study determined the dynamic change of adiponectin (APN, a cardioprotective adipokine), its receptor expression, and their impact upon myocardial ischemia/reperfusion (MI/R) injury during type 1 diabetes mellitus (T1DM) progression, and involved underlying mechanisms. Diabetic state was induced in mice via multiple intraperitoneal injections of low-dose streptozotocin. The dynamic change of plasma APN concentration and cardiac APN receptor-1 and -2 (AdipoR1/2) expression were assessed immediately after diabetes onset (0 wk) and 1, 3, 5, and 7 wk thereafter. Indicators of MI/R injury (infarct size, apoptosis, and LDH release) were determined at 0, 1, and 7 wk of DM duration. The effect of APN on MI/R injury was determined in mice subjected to different diabetic durations. Plasma APN levels (total and HMW form) increased, whereas cardiac AdipoR1 expression decreased early after T1DM onset. With T1DM progression, APN levels were reduced and cardiac AdipoR1 expression increased. MI/R injury was exacerbated with T1DM progression in a time-dependent manner. Administration of globular APN (gAD) failed to attenuate MI/R injury in 1-wk T1DM mice, while an AMP-activated protein kinase (AMPK) activator (AICAR) reduced MI/R injury. However, administration of gAD (and AICAR) reduced infarct size and cardiomyocyte apoptosis in 7-wk T1DM mice. In conclusion, our results demonstrate a dynamic dysfunction of APN/AdipoR1 during T1DM progression. Reduced cardiac AdipoR1 expression and APN concentration may be responsible for increased I/R injury susceptibility at early and late T1DM stages, respectively. Interventions bolstering AdipoR1 expression during early T1DM stages and APN supplementation during advanced T1DM stages may potentially reduce the myocardial ischemic injury in diabetic patients.

scholarly journals Exercise and Cardioprotection: A Natural Defense Against Lethal Myocardial Ischemia–Reperfusion Injury and Potential Guide to Cardiovascular Prophylaxis

2018 ◽  
Vol 24 (1) ◽  
pp. 18-30 ◽  
Author(s):  
Mohammed Andaleeb Chowdhury ◽  
Haden K. Sholl ◽  
Megan S. Sharrett ◽  
Steven T. Haller ◽  
Christopher C. Cooper ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Beneficial Effects ◽  
Natural Defense ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Similar to ischemic preconditioning, high-intensity exercise has been shown to decrease infarct size following myocardial infarction. In this article, we review the literature on beneficial effects of exercise, exercise requirements for cardioprotection, common methods utilized in laboratories to study this phenomenon, and discuss possible mechanisms for exercise-mediated cardioprotection.

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.

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