scholarly journals Polypeptide Globular Adiponectin Ameliorates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting Both Apoptosis and Necroptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Kaiyi Zhu ◽  
Jia Guo ◽  
Xiaoxue Yu ◽  
Que Wang ◽  
Chao Yan ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Specific Inhibitor ◽  
Endocrine System ◽  
Neonatal Rat ◽  
Protective Mechanisms ◽  
Lactate Dehydrogenase Release ◽  
P38mapk Signaling ◽  
Globular Adiponectin ◽  
Myocardial Ischemia Reperfusion ◽  
Hypoxia Reoxygenation

Adiponectin is a small peptide secreted and a key component of the endocrine system and immune system. Although globular adiponectin protects myocardial ischemia/reperfusion-induced cardiomyocyte injury, the protective mechanisms remain largely unresolved. Using a neonatal rat ventricular myocyte hypoxia/reoxygenation model, we investigated the role of its potential mechanisms of necroptosis in globular adiponectin-mediated protection in hypoxia/reoxygenation-induced cardiomyocyte injury as compared to apoptosis. We found that globular adiponectin treatment attenuated cardiomyocyte injury as indicated by increased cell viability and reduced lactate dehydrogenase release following hypoxia/reoxygenation. Immunofluorescence staining and Western blotting demonstrated that both necroptosis and apoptosis were triggered by hypoxia/reoxygenation and diminished by globular adiponectin. Necrostatin-1 (RIP1-specific inhibitor) and Z-VAD-FMK (pan-caspase inhibitor) only mimicked the inhibition of necroptosis and apoptosis, respectively, by globular adiponectin in hypoxia/reoxygenation-treated cardiomyocytes. Globular adiponectin attenuated reactive oxygen species production, oxidative damage, and p38MAPK and NF-κB signaling, all important for necroptosis and apoptosis. Collectively, our study suggests that globular adiponectin inhibits hypoxia/reoxygenation-induced necroptosis and apoptosis in cardiomyocytes probably by reducing oxidative stress and interrupting p38MAPK signaling.

scholarly journals CircHIPK3 regulates the autophagy and apoptosis of hypoxia/reoxygenation-stimulated cardiomyocytes via the miR-20b-5p/ATG7 axis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhimei Qiu ◽  
Yan Wang ◽  
Weiwei Liu ◽  
Chaofu Li ◽  
Ranzun Zhao ◽  
...  
Keyword(s):  
Cell Injury ◽  
Ischemia Reperfusion ◽  
Circular Rna ◽  
Control Group ◽  
Loss Of Function ◽  
Cardiomyocyte Autophagy ◽  
Myocardial Ischemia Reperfusion ◽  
Injury Research ◽  
Hypoxia Reoxygenation

AbstractAutophagy and apoptosis are involved in myocardial ischemia/reperfusion (I/R) injury. Research indicates that circular RNA HIPK3 (circHIPK3) is crucial to cell autophagy and apoptosis in various cancer types. However, the role of circHIPK3 in the regulation of cardiomyocyte autophagy and apoptosis during I/R remains unknown. Our study aimed to examine the regulatory effect of circHIPK3 during myocardial I/R and investigate its mechanism in cardiomyocyte autophagy and apoptosis. Methods and results. The expression of circHIPK3 was upregulated during myocardial I/R injury and hypoxia/reoxygenation (H/R) injury of cardiomyocytes. To study the potential role of circHIPK3 in myocardial H/R injury, we performed gain-of-function and loss-of-function analyses of circHIPK3 in cardiomyocytes. Overexpression of circHIPK3 significantly promoted H/R-induced cardiomyocyte autophagy and cell injury (increased intracellular reactive oxygen species (ROS) and apoptosis) compared to those in the control group, while silencing of circHIPK3 showed the opposite effect. Further research found that circHIPK3 acted as an endogenous miR-20b-5p sponge to sequester and inhibit miR-20b-5p activity, resulting in increased ATG7 expression. In addition, miR-20b-5p inhibitors reversed the decrease in ATG7 induced by silencing circHIPK3. Conclusions. CircHIPK3 can accelerate cardiomyocyte autophagy and apoptosis during myocardial I/R injury through the miR-20b-5p/ATG7 axis. These data suggest that circHIPK3 may serve as a potential therapeutic target for I/R.

scholarly journals Hepatic cell mobilization for protection against ischemic myocardial injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shu Q. Liu ◽  
John B. Troy ◽  
Chi-Hao Luan ◽  
Roger J. Guillory
Keyword(s):  
Ischemia Reperfusion ◽  
Hepatic Cell ◽  
Ischemic Myocardium ◽  
Cell Nuclei ◽  
Protective Mechanisms ◽  
Specific Expression ◽  
Time Points ◽  
Hepatic Cells ◽  
Cell Mobilization ◽  
Myocardial Ischemia Reperfusion

AbstractThe heart is capable of activating protective mechanisms in response to ischemic injury to support myocardial survival and performance. These mechanisms have been recognized primarily in the ischemic heart, involving paracrine signaling processes. Here, we report a distant cardioprotective mechanism involving hepatic cell mobilization to the ischemic myocardium in response to experimental myocardial ischemia–reperfusion (MI-R) injury. A parabiotic mouse model was generated by surgical skin-union of two mice and used to induce bilateral MI-R injury with unilateral hepatectomy, establishing concurrent gain- and loss-of-hepatic cell mobilization conditions. Hepatic cells, identified based on the cell-specific expression of enhanced YFP, were found in the ischemic myocardium of parabiotic mice with intact liver (0.2 ± 0.1%, 1.1 ± 0.3%, 2.7 ± 0.6, and 0.7 ± 0.4% at 1, 3, 5, and 10 days, respectively, in reference to the total cell nuclei), but not significantly in the ischemic myocardium of parabiotic mice with hepatectomy (0 ± 0%, 0.1 ± 0.1%, 0.3 ± 0.2%, and 0.08 ± 0.08% at the same time points). The mobilized hepatic cells were able to express and release trefoil factor 3 (TFF3), a protein mitigating MI-R injury as demonstrated in TFF3−/− mice (myocardium infarcts 17.6 ± 2.3%, 20.7 ± 2.6%, and 15.3 ± 3.8% at 1, 5, and 10 days, respectively) in reference to wildtype mice (11.7 ± 1.9%, 13.8 ± 2.3%, and 11.0 ± 1.8% at the same time points). These observations suggest that MI-R injury can induce hepatic cell mobilization to support myocardial survival by releasing TFF3.

A Novel Zebrafish Larvae Hypoxia/Reoxygenation Model for Assessing Myocardial Ischemia/Reperfusion Injury

Zebrafish ◽  
2019 ◽  
Vol 16 (5) ◽  
pp. 434-442
Author(s):  
Xiaoyan Zou ◽  
Qiuyan Liu ◽  
Songchang Guo ◽  
Junyi Zhu ◽  
Jichun Han ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Zebrafish Larvae ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Hypoxia Reoxygenation

scholarly journals Effects of the Delta Opioid Receptor Agonist DADLE in a Novel Hypoxia-Reoxygenation Model on Human and Rat-Engineered Heart Tissue: A Pilot Study

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1309
Author(s):  
Sandra Funcke ◽  
Tessa R. Werner ◽  
Marc Hein ◽  
Bärbel M. Ulmer ◽  
Arne Hansen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Ischemia Reperfusion ◽  
Heart Tissue ◽  
Contractile Force ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Engineered Heart Tissue ◽  
Hypoxia Reoxygenation

Intermittent hypoxia and various pharmacological compounds protect the heart from ischemia reperfusion injury in experimental approaches, but the translation into clinical trials has largely failed. One reason may lie in species differences and the lack of suitable human in vitro models to test for ischemia/reperfusion. We aimed to develop a novel hypoxia-reoxygenation model based on three-dimensional, spontaneously beating and work performing engineered heart tissue (EHT) from rat and human cardiomyocytes. Contractile force, the most important cardiac performance parameter, served as an integrated outcome measure. EHTs from neonatal rat cardiomyocytes were subjected to 90 min of hypoxia which led to cardiomyocyte apoptosis as revealed by caspase 3-staining, increased troponin I release (time control vs. 24 h after hypoxia: cTnI 2.7 vs. 6.3 ng/mL, ** p = 0.002) and decreased contractile force (64 ± 6% of baseline) in the long-term follow-up. The detrimental effects were attenuated by preceding the long-term hypoxia with three cycles of 10 min hypoxia (i.e., hypoxic preconditioning). Similarly, [d-Ala2, d-Leu5]-enkephalin (DADLE) reduced the effect of hypoxia on force (recovery to 78 ± 5% of baseline with DADLE preconditioning vs. 57 ± 5% without, p = 0.012), apoptosis and cardiomyocyte stress. Human EHTs presented a comparable hypoxia-induced reduction in force (55 ± 5% of baseline), but DADLE failed to precondition them, likely due to the absence of δ-opioid receptors. In summary, this hypoxia-reoxygenation in vitro model displays cellular damage and the decline of contractile function after hypoxia allows the investigation of preconditioning strategies and will therefore help us to understand the discrepancy between successful conditioning in vitro experiments and its failure in clinical trials.

scholarly journals Knockdown of Tripartite Motif 8 Protects H9C2 Cells Against Hypoxia/Reoxygenation-Induced Injury Through the Activation of PI3K/Akt Signaling Pathway

2020 ◽  
Vol 29 ◽  
pp. 096368972094924
Author(s):  
Xiaoyan Dang ◽  
Yong Qin ◽  
Changwei Gu ◽  
Jiangli Sun ◽  
Rui Zhang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
H9c2 Cells ◽  
Loss Of Function ◽  
Akt Signaling Pathway ◽  
Tripartite Motif ◽  
Myocardial Ischemia Reperfusion ◽  
Hypoxia Reoxygenation

Tripartite motif 8 (TRIM8) is a member of the TRIM protein family that has been found to be implicated in cardiovascular disease. However, the role of TRIM8 in myocardial ischemia/reperfusion (I/R) has not been investigated. We aimed to explore the effect of TRIM8 on cardiomyocyte H9c2 cells exposed to hypoxia/reoxygenation (H/R). We found that TRIM8 expression was markedly upregulated in H9c2 cells after stimulation with H/R. Gain- and loss-of-function assays proved that TRIM8 knockdown improved cell viability of H/R-stimulated H9c2 cells. In addition, TRIM8 knockdown suppressed reactive oxygen species production and elevated the levels of superoxide dismutase and glutathione peroxidase. Knockdown of TRIM8 suppressed the caspase-3 activity, as well as caused significant increase in bcl-2 expression and decrease in bax expression. Furthermore, TRIM8 overexpression exhibited apposite effects with knockdown of TRIM8. Finally, knockdown of TRIM8 enhanced the activation of PI3K/Akt signaling pathway in H/R-stimulated H9c2 cells. Inhibition of PI3K/Akt by LY294002 reversed the effects of TRIM8 knockdown on cell viability, oxidative stress, and apoptosis of H9c2 cells. These present findings defined TRIM8 as a therapeutic target for attenuating and preventing myocardial I/R injury.

Isoflurane Attenuates Early Neutrophil-independent Hypoxia-Reoxygenation Injuries in the Reperfused Liver in Fasted Rats

1997 ◽  
Vol 86 (1) ◽  
pp. 128-136 ◽  
Author(s):  
Shinpei Kon ◽  
Mie Imai ◽  
Hideo Inaba
Keyword(s):  
Lactate Dehydrogenase ◽  
Kupffer Cells ◽  
Minimum Alveolar Concentration ◽  
Ischemia Reperfusion ◽  
Gas Mixture ◽  
Superoxide Generation ◽  
Lactate Dehydrogenase Release ◽  
Carbon Dioxide Gas ◽  
Reoxygenation Injury ◽  
Hypoxia Reoxygenation

Background Ischemia-hypoxia followed by reperfusion and reoxygenation injures cells and organs. Previous studies have indicated that isoflurane may protect organs from ischemia-reperfusion or hypoxia-reoxygenation. This study investigated the ability of isoflurane to protect the liver from hypoxia-reoxygenation injury and the mechanisms of this phenomenon. Methods The isolated liver was perfused at a constant pressure of 12 cm H2O with a modified Krebs-Ringer-bicarbonate solution saturated with a 95% oxygen/5% carbon dioxide gas mixture. Hypoxic perfusion produced by decreasing the oxygen concentration in the gas mixture to 10% was followed by perfusion at 95% oxygen for 60 min. Viability of the liver was assessed by lactate dehydrogenase release from the liver. Isoflurane at 0.5, 1, and 2 minimum alveolar concentration was administered to assess the effect of isoflurane on hypoxia-reperfusion injury. To determine the effect of isoflurane on extracellular generation of superoxide in the liver, the reduction of ferricytochrome c with or without superoxide dismutase was measured. Results Lactate dehydrogenase release was transiently but dramatically increased by reoxygenation and significantly attenuated by 1 and 2 minimum alveolar concentration of isoflurane. Suppression of Kupffer cells with gadolinium chloride also attenuated the lactate dehydrogenase release. Isoflurane significantly reduced the superoxide generation on reperfusion. Conclusions The results show that isoflurane protected the liver from an early reoxygenation injury presumably mediated by Kupffer cells. The mechanisms of the inhibitory effects of isoflurane on the injury may involve suppression of extracellular superoxide generation during reoxygenation.

scholarly journals Cox-2 Negatively Affects the Protective Role of Propofol against Hypoxia/Reoxygenation Induced Cardiomyocytes Apoptosis through Suppressing Akt Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Kangmu Ma ◽  
Jiapei Qiu ◽  
Mi Zhou ◽  
Yang Yang ◽  
Xiaofeng Ye
Keyword(s):  
Protective Effect ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Akt Phosphorylation ◽  
Over Expression ◽  
H9c2 Cardiomyocytes ◽  
Cox 2 ◽  
Myocardial Ischemia Reperfusion ◽  
Hypoxia Reoxygenation

Nowadays, the prevention of severe myocardium injury resulting from myocardial ischemia/reperfusion injury (I/R) has been recognized as an important subject in the field of ischemic heart disease. In this study, H9c2 cardiomyocytes were exposed to cycles of hypoxia/reoxygenation (H/R) to mimic myocardial I/R injury. Western blot analysis and qRT-PCR were performed to detect the expression of Cox-2, Akt and p-Akt. Cell viability, LDH release and activity of Caspase-3 were assessed to determine the protective effect of propofol. The results proved that the protective effect of propofol for H/R challenged cardiomyocytes was associated with Akt phosphorylation. We also revealed that treatment of propofol suppressed the expression of Cox-2 in cardiomyocytes which was up-regulated after H/R treatment. Conversely, the over-expression of Cox-2 inhibited Akt phosphorylation while enhancing cardiomyocytes apoptosis. Interestingly, Akt activator exhibited similar protective effect with propofol and could diminish the influences brought by over-expression of Cox-2. Thus, it could be concluded that Cox-2 negatively affects the protective effect of propofol against hypoxia/reoxygenation induced cardiomyocyte apoptosis by suppressing Akt phosphorylation.

Heart and Mitochondria: Pathophysiology and Implications for Cardiac Surgeons

2017 ◽  
Vol 66 (01) ◽  
pp. 011-019 ◽  
Author(s):  
Michael Schwarzer ◽  
Susanne Rohrbach ◽  
Bernd Niemann
Keyword(s):  
Cardiac Surgery ◽  
Ischemia Reperfusion ◽  
Systemic Circulation ◽  
Cardiac Damage ◽  
Protective Mechanisms ◽  
Ischemic Conditioning ◽  
Disease States ◽  
Similar Disease ◽  
Myocardial Ischemia Reperfusion ◽  
Cardiac Surgeons

Excluding the heart from systemic circulation during cardiac surgery renders the myocardium ischemic, resulting in cardiac damage. In addition, another hit to the myocardium will occur upon restoration of blood flow, in the reperfusion phase. Experimental data from animal models have revealed that loss of cardiac metabolic flexibility and mitochondrial dysfunctions contributes to contractile impairment in hypertrophied, failing, obese, and diabetic hearts. Such diseased hearts are prone to myocardial ischemia–reperfusion (I/R) injury. Although analyses in human cardiac samples are not as comprehensive as animal data, similar disease-associated metabolic and mitochondrial changes exist. Considering increasing age and comorbidities in patients nowadays, it is not surprising that I/R injuries remain a major cause of morbidity and mortality after cardiac surgery. Mitochondria have emerged as critical targets but also key regulators of myocardial I/R injury, and the extent of mitochondrial damage is a major determinant of myocardial I/R injury. Although cardioprotective mechanisms are diverse, many come together and involve steps at the point of mitochondria. We will, therefore, provide a description of mitochondrial alterations observed in various cardiac disease states and discuss the current experimental knowledge of the role of mitochondria in I/R and of potential protective mechanisms against myocardial I/R injury involving mitochondria. Within this review, we will focus on the protection against I/R injury conferred by caloric restriction (CR) and by ischemic conditioning. Further research is needed to establish whether strategies targeting mitochondria, which have been proposed from preclinical studies, could be translated into cardioprotective therapies against I/R injury in patients.

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