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European Journal of Pharmacology Aug 2023Acute lung injury (ALI) is a life-threatening complication of cardiac surgery that has a high rate of morbidity and mortality. Epithelial ferroptosis is believed to be...
Acute lung injury (ALI) is a life-threatening complication of cardiac surgery that has a high rate of morbidity and mortality. Epithelial ferroptosis is believed to be involved in the pathogenesis of ALI. MOTS-c has been reported to play a role in regulating inflammation and sepsis-associated ALI. The purpose of this study is to observe the effect of MOTS-c on myocardial ischemia reperfusion (MIR)-induced ALI and ferroptosis. In humans, we used ELISA kits to investigate MOTS-c and malondialdehyde (MDA) levels in patients undergoing off-pump coronary artery bypass grafting (CABG). In vivo, we pretreated Sprague-Dawley rats with MOTS-c, Ferrostatin-1 and Fe-citrate(Ⅲ). We conducted Hematoxylin and Eosin (H&E) staining and detection of ferroptosis-related genes in MIR-induced ALI rats. In vitro, we evaluated the effect of MOTS-c on hypoxia regeneration (HR)-induced mouse lung epithelial-12 (MLE-12) ferroptosis and analyzed the expression of PPARγ through western blotting. We found that circulating MOTS-c levels were decreased in postoperative ALI patients after off-pump CABG, and that ferroptosis contributed to ALI induced by MIR in rats. MOTS-c suppressed ferroptosis and alleviated ALI induced by MIR, and the protective effect of MOTS-c- was dependent on PPARγ signaling pathway. Additionally, HR promoted ferroptosis in MLE-12 cells, and MOTS-c inhibited ferroptosis against HR through the PPARγ signaling pathway. These findings highlight the therapeutic potential of MOTS-c for improving postoperative ALI induced by cardiac surgery.
Topics: Humans; Mice; Rats; Animals; Ferroptosis; PPAR gamma; Myocardial Reperfusion Injury; Rats, Sprague-Dawley; Signal Transduction; Coronary Artery Disease; Transcription Factors; Ischemia; Acute Lung Injury; Peptides; Reperfusion Injury
PubMed: 37290680
DOI: 10.1016/j.ejphar.2023.175835 -
International Journal of Molecular... Mar 2021Pharmacologic cardiac conditioning increases the intrinsic resistance against ischemia and reperfusion (I/R) injury. The cardiac conditioning response is mediated via... (Review)
Review
Pharmacologic cardiac conditioning increases the intrinsic resistance against ischemia and reperfusion (I/R) injury. The cardiac conditioning response is mediated via complex signaling networks. These networks have been an intriguing research field for decades, largely advancing our knowledge on cardiac signaling beyond the conditioning response. The centerpieces of this system are the mitochondria, a dynamic organelle, almost acting as a cell within the cell. Mitochondria comprise a plethora of functions at the crossroads of cell death or survival. These include the maintenance of aerobic ATP production and redox signaling, closely entwined with mitochondrial calcium handling and mitochondrial permeability transition. Moreover, mitochondria host pathways of programmed cell death impact the inflammatory response and contain their own mechanisms of fusion and fission (division). These act as quality control mechanisms in cellular ageing, release of pro-apoptotic factors and mitophagy. Furthermore, recently identified mechanisms of mitochondrial regeneration can increase the capacity for oxidative phosphorylation, decrease oxidative stress and might help to beneficially impact myocardial remodeling, as well as invigorate the heart against subsequent ischemic insults. The current review highlights different pathways and unresolved questions surrounding mitochondria in myocardial I/R injury and pharmacological cardiac conditioning.
Topics: Adenosine Triphosphate; Animals; Cell Death; Humans; Ischemic Preconditioning, Myocardial; Mitochondria; Mitochondrial Dynamics; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; Oxidative Phosphorylation; Oxidative Stress; Regeneration; Signal Transduction; Translational Research, Biomedical
PubMed: 33810024
DOI: 10.3390/ijms22063224 -
Aging and Disease May 2024Myocardial ischemia is the most common cardiovascular disease. Reperfusion, an important myocardial ischemia tool, causes unexpected and irreversible damage to... (Review)
Review
Myocardial ischemia is the most common cardiovascular disease. Reperfusion, an important myocardial ischemia tool, causes unexpected and irreversible damage to cardiomyocytes, resulting in myocardial ischemia/reperfusion (MI/R) injury. Upon stress, especially oxidative stress induced by reactive oxygen species (ROS), autophagy, which degrades the intracellular energy storage to produce metabolites that are recycled into metabolic pathways to buffer metabolic stress, is initiated during myocardial ischemia and MI/R injury. Excellent cardioprotective effects of autophagy regulators against MI and MI/R have been reported. Reversing disordered cardiac metabolism induced by ROS also exhibits cardioprotective action in patients with myocardial ischemia. Herein, we review current knowledge on the crosstalk between ROS, cardiac autophagy, and metabolism in myocardial ischemia and MI/R. Finally, we discuss the possible regulators of autophagy and metabolism that can be exploited to harness the therapeutic potential of cardiac metabolism and autophagy in the diagnosis and treatment of myocardial ischemia and MI/R.
Topics: Humans; Autophagy; Reactive Oxygen Species; Myocardial Reperfusion Injury; Myocardial Ischemia; Animals; Oxidative Stress
PubMed: 37728583
DOI: 10.14336/AD.2023.0823-4 -
Pharmacology Research & Perspectives Aug 2021Myocardial ischemia continues to be the first cause of morbimortality in the world; the definitive treatment is reperfusion; however, this action causes additional...
Myocardial ischemia continues to be the first cause of morbimortality in the world; the definitive treatment is reperfusion; however, this action causes additional damage to ischemic myocardial tissue; this forces to seek therapies of cardioprotection to reduce this additional damage. There are many cardioprotective agents; within these, cannabinoids have shown to have beneficial effects, mainly cannabidiol (CBD). CBD is a non psychoactive cannabinoid. To evaluate the effect in experimental models of CBD in myocardial ischemia reperfusion in rats, twelve-week-old male rats have been used. The animals were divides in 3 groups: control(C), ischemia reperfusion (IR) and CBD pretreatment (1/day/5mg/kg /10days). Langendorff organ isolate studies were performed, and the area of infarction was assessed with triphenyl tetrazolium, in addition to molecular analysis of AT1 and AT2 receptors and Akt and Erk proteins and their phosphorylated forms related to RISK pathways. It was observed that there is an improvement with the use of CBD increasing inotropism and cardiac lusitropism, improving considerably the cardiovascular functionality. These could be related to the reduction of the area of infarction and activation of the AT2 receptor and the RISK pathway with absence of activation of the AT2 receptor (these could relate the reduction of the infarct area and the restoration of cardiovascular function with the activation of the AT2 receptor and the RISK pathway with the absence of activation of the AT2 receptor). The use of cannabinoids was shown to have beneficial effects when used as a treatment for myocardial reperfusion damage.
Topics: Animals; Cannabidiol; Cardiotonic Agents; Heart; Hemodynamics; In Vitro Techniques; MAP Kinase Signaling System; Male; Myocardial Reperfusion Injury; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Ventricular Function, Left; Rats
PubMed: 34176244
DOI: 10.1002/prp2.784 -
Frontiers in Endocrinology 2023The incidence of diabetes and related mortality rate increase yearly in modern cities. Additionally, elevated glucose levels can result in an increase of reactive oxygen... (Review)
Review
The incidence of diabetes and related mortality rate increase yearly in modern cities. Additionally, elevated glucose levels can result in an increase of reactive oxygen species (ROS), ferroptosis, and the disruption of protective pathways in the heart. These factors collectively heighten the vulnerability of diabetic individuals to myocardial ischemia. Reperfusion therapies have been effectively used in clinical practice. There are limitations to the current clinical methods used to treat myocardial ischemia-reperfusion injury. As a result, reducing post-treatment ischemia/reperfusion injury remains a challenge. Therefore, efforts are underway to provide more efficient therapy. Salvia miltiorrhiza Bunge (Danshen) has been used for centuries in ancient China to treat cardiovascular diseases (CVD) with rare side effects. Salvianolic acid is a water-soluble phenolic compound with potent antioxidant properties and has the greatest hydrophilic property in Danshen. It has recently been discovered that salvianolic acids A (SAA) and B (SAB) are capable of inhibiting apoptosis by targeting the JNK/Akt pathway and the NF-κB pathway, respectively. This review delves into the most recent discoveries regarding the therapeutic and cardioprotective benefits of salvianolic acid for individuals with diabetes. Salvianolic acid shows great potential in myocardial protection in diabetes mellitus. A thorough understanding of the protective mechanism of salvianolic acid could expand its potential uses in developing medicines for treating diabetes mellitus related myocardial ischemia-reperfusion.
Topics: Humans; Myocardial Reperfusion Injury; Heart; Myocardium; Diabetes Mellitus; Alkenes; Polyphenols
PubMed: 38283744
DOI: 10.3389/fendo.2023.1322474 -
Arquivos Brasileiros de Cardiologia Jul 2021
Topics: Humans; Myocardial Infarction; Myocardial Reperfusion; Thrombolytic Therapy
PubMed: 34320082
DOI: 10.36660/abc.20210500 -
European Journal of Medical Research Feb 2023Reperfusion modality can cause damage to cardiomyocytes, known as myocardial ischemia-reperfusion injury (MI/RI). Circular RNAs (circRNAs) are fundamental regulators...
Reperfusion modality can cause damage to cardiomyocytes, known as myocardial ischemia-reperfusion injury (MI/RI). Circular RNAs (circRNAs) are fundamental regulators associated with many cardiac diseases, including MI/RI. However, their functional impact on cardiomyocyte fibrosis and apoptosis remains elusive. Therefore, this study aimed to explore possible molecular mechanisms of circARPA1 in animal models and in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. GEO dataset analysis showed that has_circ_0023461 (circARPA1) was differentially expressed in myocardial infarction samples. Real-time quantitative PCR further supported that circARPA1 was expressed at high levels in animal models and in H/R-triggered cardiomyocytes. Then, loss-of-function assays were performed to show that circARAP1 suppression effectively ameliorated cardiomyocyte fibrosis and apoptosis in MI/RI mice. Mechanistic experiments showed that miR-379-5p, KLF9 and Wnt signaling pathways were associated with circARPA1. circARPA1 can sponge miR-379-5p to regulate KLF9 expression, thereby activating the wnt/β-catenin pathway. Finally, gain-of-function assays revealed that circARAP1 aggravated MI/RI in mice and H/R-induced cardiomyocyte injury by regulating the miR-379-5p/KLF9 axis to activate Wnt/β-catenin signaling.
Topics: Animals; Mice; Apoptosis; beta Catenin; Hypoxia; MicroRNAs; Myocardial Reperfusion Injury; Myocytes, Cardiac; Wnt Signaling Pathway; RNA, Circular
PubMed: 36803446
DOI: 10.1186/s40001-023-01001-0 -
Disease Markers 2022To investigate the role of leptin in regulating cell inflammation and protecting myocardium after myocardial ischemia-reperfusion injury in rats through signaling...
OBJECTIVE
To investigate the role of leptin in regulating cell inflammation and protecting myocardium after myocardial ischemia-reperfusion injury in rats through signaling pathway at tissue and molecular protein levels.
METHODS
Healthy female SD rats were randomly divided into 4 groups, which were sham, I/R group, leptin low-dose intervention group, and high-dose intervention group (40 g/kg and 80 g/kg, respectively). Cardiac hemodynamics, myocardial enzymology, inflammatory indices, and pathological changes were observed. Western blot was used to observe the expression of PI3K, AKT, and NFB protein by leptin.
RESULTS
Leptin can improve the hemodynamics of cardiac ischemia-reperfusion rats, improve the expression of myocardial enzymology, reduce the release of cardiac and serum inflammatory factors, increased PI3k, AKT, and NFB expression, and reduce the occurrence of inflammation from the perspective of gross pathology, thus protecting the body.
CONCLUSION
Leptin pretreatment can reduce MIRI injury, and the protective mechanism may be that leptin upregulates PI3K-AKT-NFB expression in myocardial tissue to reduce inflammation and promote repair of I/R injury.
Topics: Animals; Class Ib Phosphatidylinositol 3-Kinase; Female; Inflammation; Leptin; Myocardial Reperfusion Injury; Myocardium; Phosphatidylinositol 3-Kinases; Protective Agents; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction
PubMed: 35308138
DOI: 10.1155/2022/8707061 -
Journal of Cellular and Molecular... Mar 2020Mitochondrial fusion and fission dynamic are critical to the myocardial protection against ischaemia-reperfusion injury. Notch1 signalling plays an important role in...
Mitochondrial fusion and fission dynamic are critical to the myocardial protection against ischaemia-reperfusion injury. Notch1 signalling plays an important role in heart development, maturation and repair. However, the role of Notch1 in the myocardial mitochondrial fusion and fission dynamic remains elusive. Here, we isolated myocardial cells from rats and established myocardial ischaemia-reperfusion injury (IRI) model. We modulated Notch1, MFN1 and DRP1 expression levels in myocardial cells via infection with recombinant adenoviruses. The results showed that Notch1 improves the cell viability and mitochondrial fusion in myocardiocytes exposed to IRI. These improvements were dependent on the regulation of MFN1 and DRP1. On the mechanism, we found that MNF1 is transcriptionally activated by RBP-Jk in myocardiocytes. Notch1 also improves the mitochondrial membrane potential in myocardiocytes exposed to IRI. Moreover, we further confirmed the protection of the Notch1-MFN1/Drp1 axis on the post-ischaemic recovery of myocardial performance is associated with the preservation of the mitochondrial structure. In conclusion, this study presented a detailed mechanism by which Notch1 signalling improves mitochondrial fusion during myocardial protection.
Topics: Animals; Apoptosis; Cell Survival; Dynamins; GTP Phosphohydrolases; Gene Expression Regulation; Male; Membrane Potential, Mitochondrial; Mitochondria, Heart; Mitochondrial Dynamics; Mitochondrial Membrane Transport Proteins; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; Protective Agents; Rats; Receptor, Notch1; Signal Transduction
PubMed: 31975567
DOI: 10.1111/jcmm.14992 -
BioMed Research International 2020This project is aimed at investigating whether CircANXA2 can promote the apoptosis of myocardial cells by inhibiting miR-133 expression and thereby participate in the...
OBJECTIVE
This project is aimed at investigating whether CircANXA2 can promote the apoptosis of myocardial cells by inhibiting miR-133 expression and thereby participate in the development of myocardial ischemia-reperfusion injury. . Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of CircANXA2 in H9c2 cells after hypoxia/reoxygenation (H/R) treatment. Evaluation of myocardial injury markers in H9c2 cells was performed using commercial kits, including lactate dehydrogenase (LDH), malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidation (GSH-PX). MTT analysis and flow cytometry were used to detect myocardial cell proliferation and apoptosis, respectively. Western blot was used to detect the protein expression of apoptosis-related genes.
RESULT
qRT-PCR results showed that compared with the control, the expression of CircANXA2 was upregulated and the expression level of miR-133 was significantly decreased in H/R-treated H9c2 cells. CircANXA2 overexpression increased LDH, MDA, SOD, and GSH-PX activity in H/R-treated H9c2 cells. At the same time, CircANXA2 overexpression inhibited the proliferation of H/R-treated cells, and CircANXA2 was able to induce cardiomyocyte apoptosis. Western blot results showed that after overexpression of CircANXA2, the proapoptotic genes Bax and cytochrome C was upregulated, while the antiapoptotic gene Bcl-2 was downregulated. In H9c2 cells, upregulating miR-133 can reverse the inhibition of proliferation induced by CircANXA2 overexpression and increase apoptosis.
CONCLUSIONS
CircANXA2 promotes cardiomyocyte apoptosis in myocardial ischemia-reperfusion injury by inhibiting the expression of miR-133. CircANXA2 may be a potential target for myocardial ischemia-reperfusion injury.
Topics: Animals; Apoptosis; Cell Line; Gene Expression Regulation; MicroRNAs; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; RNA, Circular; Rats
PubMed: 32685535
DOI: 10.1155/2020/8590861