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Oxidative Medicine and Cellular... 2021Ferroptosis is a newly discovered form of regulated cell death dependent on iron and reactive oxygen species (ROS). It directly or indirectly affects the activity of... (Review)
Review
Ferroptosis is a newly discovered form of regulated cell death dependent on iron and reactive oxygen species (ROS). It directly or indirectly affects the activity of glutathione peroxidases (GPXs) under the induction of small molecules, causing membrane lipid peroxidation due to redox imbalances and excessive ROS accumulation, damaging the integrity of cell membranes. Ferroptosis is mainly characterized by mitochondrial shrinkage, increased density of bilayer membranes, and the accumulation of lipid peroxidation. Myocardial ischemia-reperfusion injury (MIRI) is an unavoidable risk event for acute myocardial infarction. Ferroptosis is closely associated with MIRI, and this relationship is discussed in detail here. This review systematically summarizes the process of ferroptosis and the latest research progress on the role of ferroptosis in MIRI to provide new ideas for the prevention and treatment of MIRI.
Topics: Animals; Ferroptosis; Glutathione Peroxidase; Humans; Iron; Lipid Peroxidation; Mitochondria, Heart; Myocardial Reperfusion Injury; Myocardium; Reactive Oxygen Species; Signal Transduction
PubMed: 34725566
DOI: 10.1155/2021/9929687 -
Biomedicine & Pharmacotherapy =... Oct 2022The present study aimed to investigate whether dexmedetomidine (Dex) exerts cardioprotection effect through inhibiting ferroptosis. Myocardial ischemia/reperfusion...
The present study aimed to investigate whether dexmedetomidine (Dex) exerts cardioprotection effect through inhibiting ferroptosis. Myocardial ischemia/reperfusion injury (MIRI) was induced in Sprague-Dawley rats in Langendorff preparation. The hemodynamic parameters were recorded. Triphenyltetrazolium chloride (TTC) staining was used to determine infarct size. In the in vitro study, the model of hypoxia/reoxygenation (HR) was established in H9c2 cells. Cell viability and apoptosis were detected using cell counting kit 8 (CCK-8), and AV/PI dual staining respectively. Lipid peroxidation as measured by the fluorescence of the fatty acid analog C11-BODIPY581/591 probe and intracellular ferrous iron levels were measured by fluorescence of Phen Green SK (PGSK) probe, whereas immunofluorescence and transmission electron microscopy were also used to examine ferroptosis. Protein levels were investigated by Western blot. The interactions of AMPK/GSK-3β signaling with Nrf2 were also assessed through AMPK inhibition and GSK-3β overexpression. Our findings indicated that Dex significantly alleviated myocardial infarction, improved heart function, and decreased HR-induced accumulation of Fe and lipid peroxidation in cardiomyocytes. Dex significantly increased the expression levels of Nrf2, SLC7A11, and GPX4. However, inhibition of Nrf2 by ML385 blunted the protective effect of Dex in HR-treated H9c2 cells. Inhibition of AMPK with a specific inhibitor or siRNA decreased the expression levels of phosphorylation of GSK-3β and Nrf2 induced by Dex. Overexpression of GSK-3β resulted in lower levels of nuclear Nrf2, whereas depression of GSK-3β enhanced expressions of nuclear Nrf2. In conclusion, Dex protects hearts against MIRI-induced ferroptosis via activation of Nrf2 through AMPK/GSK-3β signaling pathway.
Topics: Animals; Rats; AMP-Activated Protein Kinases; Apoptosis; Dexmedetomidine; Ferroptosis; Glycogen Synthase Kinase 3 beta; Myocardial Ischemia; Myocardial Reperfusion Injury; NF-E2-Related Factor 2; Rats, Sprague-Dawley
PubMed: 35988428
DOI: 10.1016/j.biopha.2022.113572 -
Molecular Medicine Reports May 2021Myocardial ischemia‑reperfusion injury (MIRI) is a severe injury to the ischemic myocardium following the recovery of blood flow. Currently, there is no effective... (Review)
Review
Myocardial ischemia‑reperfusion injury (MIRI) is a severe injury to the ischemic myocardium following the recovery of blood flow. Currently, there is no effective treatment for MIRI in clinical practice. Over the past two decades, biological studies of hypoxia and hypoxia‑inducible factor‑1α (HIF‑1α) have notably improved understanding of oxygen homeostasis. HIF‑1α is an oxygen‑sensitive transcription factor that mediates adaptive metabolic responses to hypoxia and serves a pivotal role in MIRI. In particular, previous studies have demonstrated that HIF‑1α improves mitochondrial function, decreases cellular oxidative stress, activates cardioprotective signaling pathways and downstream protective genes and interacts with non‑coding RNAs. The present review summarizes the roles and associated mechanisms of action of HIF‑1α in MIRI. In addition, HIF‑1α‑associated MIRI intervention, including natural compounds, exosomes, ischemic preconditioning and ischemic post‑processing are presented. The present review provides evidence for the roles of HIF‑1α activation in MIRI and supports its use as a therapeutic target.
Topics: Apoptosis; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Ischemic Preconditioning; Mitochondria; Myocardial Reperfusion Injury; Reperfusion Injury; Signal Transduction
PubMed: 33760122
DOI: 10.3892/mmr.2021.11991 -
Journal of Cardiology Feb 2023Owing to recent advances in early reperfusion strategies, pharmacological therapy, standardized care, and the identification of vulnerable patient subsets, the prognosis... (Review)
Review
Owing to recent advances in early reperfusion strategies, pharmacological therapy, standardized care, and the identification of vulnerable patient subsets, the prognosis of acute myocardial infarction has improved. However, there is still considerable room for improvement. This review article summarizes the latest evidence concerning clinical diagnosis and treatment of acute myocardial infarction.
Topics: Humans; Myocardial Infarction; Myocardial Reperfusion; Thrombolytic Therapy; Prognosis; Percutaneous Coronary Intervention; Treatment Outcome; Myocardial Revascularization
PubMed: 35882613
DOI: 10.1016/j.jjcc.2022.07.003 -
Biochimica Et Biophysica Acta.... Jul 2020Despite major progress in interventional and medical treatments, myocardial infarction (MI) and subsequent development of heart failure (HF) are still associated with... (Review)
Review
Despite major progress in interventional and medical treatments, myocardial infarction (MI) and subsequent development of heart failure (HF) are still associated with high mortality. Both during ischemia reperfusion (IR) in the acute setting of MI, as well as in the chronic remodeling process following MI, oxidative stress substantially contributes to cardiac damage. Reactive oxygen species (ROS) generated within mitochondria are particular drivers of mechanisms contributing to IR injury, including induction of mitochondrial permeability transition or oxidative damage of intramitochondrial structures and molecules. But even beyond the acute setting, mechanisms like inflammatory signaling, extracellular remodeling, or pro-apoptotic signaling that contribute to post-infarction remodeling are regulated by mitochondrial ROS. In the current review, we discuss both sources and consequences of mitochondrial ROS during IR and in the chronic setting following MI, thereby emphasizing the potential therapeutic value of attenuating mitochondrial ROS to improve outcome and prognosis for patients suffering MI.
Topics: Apoptosis; Heart Failure; Humans; Mitochondria; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Oxidative Stress; Reactive Oxygen Species; Ventricular Remodeling
PubMed: 32173461
DOI: 10.1016/j.bbadis.2020.165768 -
Intensive Care Medicine Apr 2021The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care...
The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care guidelines for adults, which are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. The topics covered include the post-cardiac arrest syndrome, diagnosis of cause of cardiac arrest, control of oxygenation and ventilation, coronary reperfusion, haemodynamic monitoring and management, control of seizures, temperature control, general intensive care management, prognostication, long-term outcome, rehabilitation and organ donation.
Topics: Adult; Cardiopulmonary Resuscitation; Critical Care; Heart Arrest; Humans; Myocardial Reperfusion; Resuscitation; Seizures
PubMed: 33765189
DOI: 10.1007/s00134-021-06368-4 -
Biomedicine & Pharmacotherapy =... Dec 2019The study was established to inquire into the protective effect of the HIF-1α (Hypoxia-inducible factor-1α)/ BNIP3(Bcl-2/adenovirus E1B 19-kDa interacting protein)...
OBJECTIVE
The study was established to inquire into the protective effect of the HIF-1α (Hypoxia-inducible factor-1α)/ BNIP3(Bcl-2/adenovirus E1B 19-kDa interacting protein) signal path-induced-autophagy during myocardial ischemia/ reperfusion (I/R) and oxygen-glucose deprivation/recovery (OGD/R) injury in heart-derived H9C2 cells as well as its potential underlying mechanism.
METHODS
Immediate myocardial I/R in SD (Spraque Dawley) rats and cytotoxicity of OGD/R injury on H9C2 cells with and without inhibitors or agonists of HIF-1α and BNIP3 were evaluated. Expression of mitochondrial autophagic protein were detected by Western blot and immunofluorescence. And the mitochondrial autophagosome were detected using Transmission Electron Microscope (TEM).
RESULTS
I/R and OGD/R injury increased the expression level of HIF-1α, activated the downstream BNIP3 and subsequently triggered mitochondria-dependent autophagy. Up-regulation the expression of HIF-1α and BNIP3 may promote the cardiac myocytes of SD rats of I/R injure and OGD/R injury-induced autophagy of H9C2 cells. Moreover, down-regulation the expression of HIF-1α or BNIP3-siRNA decreased H9C2 cells autophagy under OGD/R injury.
CONCLUSIONS
Together, our studies indicated that HIF-1α synchronization regulate BNIP3 during OGD/R injury-induced autophagy in H9C2 cells, though BNIP3-induced autophagy acting as a survival mechanism.
Topics: Amino Acids, Dicarboxylic; Animals; Apoptosis; Autophagy; Beclin-1; Cell Hypoxia; Cell Line; Hypoxia-Inducible Factor 1, alpha Subunit; Indazoles; Male; Membrane Proteins; Microtubule-Associated Proteins; Mitochondria; Mitochondrial Proteins; Models, Animal; Myocardial Reperfusion Injury; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; Signal Transduction
PubMed: 31590128
DOI: 10.1016/j.biopha.2019.109464 -
Mediators of Inflammation 2020Myocardial ischemia reperfusion syndrome is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial infarction-derived damage... (Review)
Review
Myocardial ischemia reperfusion syndrome is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial infarction-derived damage and to heal injury. In such a setting, the establishment of an effective therapy to treat this condition has been elusive, perhaps because the experimental treatments have been conceived to block just one of the many pathogenic pathways of the disease, or because they thwart the tissue-repairing phase of the syndrome. Either way, we think that a discussion about the pathophysiology of the disease and the mechanisms of action of some drugs may shed some clarity on the topic.
Topics: Animals; Humans; Immunity, Innate; Immunosuppression Therapy; Inflammation; Inflammation Mediators; Ischemia; Mice; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Phenotype; Reperfusion Injury; Th1 Cells; Th2 Cells
PubMed: 32410868
DOI: 10.1155/2020/8405370 -
Aging Nov 2020Ischemia/reperfusion (I/R) injury is a life-threatening vascular emergency following myocardial infarction. Our previous study showed cardioprotective effects of...
Ischemia/reperfusion (I/R) injury is a life-threatening vascular emergency following myocardial infarction. Our previous study showed cardioprotective effects of metformin against myocardial I/R injury. In this study, we further examined the involvement of AMPK mediated activation of NLRP3 inflammasome in this cardioprotective effect of metformin. Myocardial I/R injury was simulated in a rat heart Langendorff model and neonatal rat ventricle myocytes (NRVMs) were subjected to hypoxi/reoxygenation (H/R) to establish an in vitro model. Outcome measures included myocardial infarct size, hemodynamic monitoring, myocardial tissue injury, myocardial apoptotic index and the inflammatory response. myocardial infarct size and cardiac enzyme activities. First, we found that metformin postconditioning can not only significantly alleviated myocardial infarct size, attenuated cell apoptosis, and inhibited myocardial fibrosis. Furthermore, metformin activated phosphorylated AMPK, decreased pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β, and decreased NLRP3 inflammasome activation. In isolated NRVMs metformin increased cellular viability, decreased LDH activity and inhibited cellular apoptosis and inflammation. Importantly, inhibition of AMPK phosphorylation by Compound C (CC) resulted in decreased survival of cardiomyocytes mainly by inducing the release of inflammatory cytokines and increasing NLRP3 inflammasome activation. Finally, in vitro studies revealed that the NLRP3 activator nigericin abolished the anti-inflammatory effects of metformin in NRVMs, but it had little effect on AMPK phosphorylation. Collectively, our study confirmed that metformin exerts cardioprotective effects by regulating myocardial I/R injury-induced inflammatory response, which was largely dependent on the enhancement of the AMPK pathway, thereby suppressing NLRP3 inflammasome activation.
Topics: AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Cells, Cultured; Cytokines; Disease Models, Animal; Enzyme Activation; Hemodynamics; Inflammasomes; Inflammation Mediators; Isolated Heart Preparation; Male; Metformin; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; NLR Family, Pyrin Domain-Containing 3 Protein; Phosphorylation; Pyroptosis; Rats, Sprague-Dawley; Signal Transduction; Ventricular Function, Left
PubMed: 33232283
DOI: 10.18632/aging.202143 -
Gene Jan 2022Resveratrol (Res) is a polyphenol with a variety of biological activities. However, whether Res can prevent myocardial ischemia-reperfusion (I/R) injury is not yet...
Resveratrol (Res) is a polyphenol with a variety of biological activities. However, whether Res can prevent myocardial ischemia-reperfusion (I/R) injury is not yet known. This study aimed to investigate the protective effect of Res on myocardial I/R injury and to explore its potential mechanism. H9c2 cells were used for the in vitro experiments and oxygen-glucose deprivation/reoxygenation (OGD/R) model was established. Rats were ligated and perfused by the left anterior descending branch with or without Res (50 mg/kg·bw) for 14 days.The higher level of oxidative stress and Fe content was observed in OGD/R-induced H9c2 cells than that of normal cells. OGD/R-induced H9c2 cells showed increased ferroptosis, mainly by reducing the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1), but enhancing the expression of transferrin receptor 1 (TfR1). Both in vivo and in vitro experiments indicated that Res reduced the level of oxidative stress and Fe2 + content. In addition, Res inhibited ferroptosis, decreased TfR1 expression, and increased the expressions of FTH1 and GPX4 in OGD/R-induced H9c2 cells and I/R rats. Moreover, we found that Res inhibited ferroptosis by the regulation of ubiquity specific peptidase 19 (USP19)-Beclin1 autophagy. Res protects against myocardial I/R injury via reducing oxidative stress and attenuating ferroptosis. Res could be a potential agent to the prevention of myocardial I/R injury.
Topics: Animals; Apoptosis; Autophagy; Cell Line; Cell Survival; Ferroptosis; Glucose; Heart; Male; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; Oxidative Stress; Oxygen; Protective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Resveratrol; Signal Transduction
PubMed: 34530090
DOI: 10.1016/j.gene.2021.145968