Screening of differentially expressed microRNAs in MSCexo and TSA-MSCexo
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE212320 | GEO | 2022/11/22
REPOSITORIES: GEO
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Project description:Endothelial progenitors represent one of the most promising cell-based strategies for vascular repair of ischemic tissue damage, including limb ischemia, myocardial infarction and stroke. We have shown that the transcription factor TAL1 regulates a transcription program that drives the migration and adhesion of ECFCs. Furthermore, treatment of ECFCs with the HDAC inhibitor TSA increases the expression of TAL1-dependent genes and promotes the migration, chemotaxis and adhesion of ECFCs. Finally, ex vivo treatment with TSA also improves the vascular repair properties of ECFCs in vivo when these cells are transplanted in a mouse model of hindlimb ischemia. The goal of this experiment was to test whether TSA treatment of ECFCs affect TAL1 genomic binding. TAL1 ChIP-sequencing was performed from ECFCs that have been treated or not TSA. As negative controls, we performed Mock-ChIP-seq from the same samples using normal IgG instead of the TAL1 antibody. Overall, we find that there is no change in TAL1 genomic binding in ECFCs upon TSA treatment.
2014-05-06 | E-GEOD-53423 | biostudies-arrayexpress
Project description:Endothelial progenitors represent one of the most promising cell-based strategies for vascular repair of ischemic tissue damage, including limb ischemia, myocardial infarction and stroke. We have shown that the transcription factor TAL1 regulates a transcription program that drives the migration and adhesion of ECFCs. Furthermore, treatment of ECFCs with the HDAC inhibitor TSA increases the expression of TAL1-dependent genes and promotes the migration, chemotaxis and adhesion of ECFCs. Finally, ex vivo treatment with TSA also improves the vascular repair properties of ECFCs in vivo when these cells are transplanted in a mouse model of hindlimb ischemia. The goal of this experiment was to test whether TSA treatment of ECFCs affect TAL1 genomic binding.
2014-05-06 | GSE53423 | GEO
Project description:MicroRNAs are closely associated with the pathogenesis of various diseases, but the relationship between miRNAs and myocardial ischemia–reperfusion (I/R) injury remains unclear. Therefore, we aimed to explore the role and function of miRNAs in I/R. We established hypoxia/reoxygenation (H/R) model to detect differentially expressed miRNAs using high-throughput sequencing in rat myocardial cell. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment were used to analyse the potential functions and signaling pathways of target genes. We further assessed the expression of miRNA, iron ions, reactive oxygen species, and ferroptosis markers. In the study, 113 differentially expressed miRNAs, comprising 76 and 37 up-regulated and down-regulated genes, respectively, were identified. These findings offer a novel perspective on I/R regulation, down-regulation of miRNA expression inhibits ferroptosis and alleviates myocardial damage.The specific mechanisms underlying the actions of it require further study.
2023-09-15 | GSE242888 | GEO
Project description:Purpose：Detection of differentially expressed lncRNA in the infarct zone and the control group in myocardial ischemia-reperfusion injury model tissue. Method: Use 8 weeks of C57BL/6 mice to establish a myocardial ischemia-reperfusion injury model, 45 minutes of ischemia, and 24 hours after reperfusion, the mice were sacrificed to obtain materials. Result: The expression of lncRNAs in the infarct area of myocardial ischemia-reperfusion injury model mice was detected, and it was found that a total of 43 lncRNAs related to myocardial ischemia-reperfusion injury changed in expression, of which 17 were up-regulated (fold change >1.5). 26 expressions are down-regulated (fold change <0.8)
2020-11-11 | GSE161151 | GEO
Project description:To identify the role of mRNA during myocardial ischemia-reperfusion in mice, we have employed high-throughput sequencing to detect mRNA expression. Samples were collected from the control group and the ischemia reperfusion groups , with 5 samples per group. The candidate mRNA that may affect the process of myocardial ischemia-reperfusion was screened by comparing the ischemia-reperfusion group and the control group.
2023-11-15 | GSE223343 | GEO
Project description:Heart disease remains the leading cause of death globally. Although reperfusion following myocardial ischemia can prevent death by restoring nutrient flow, ischemia/reperfusion injury can cause significant heart damage. The mechanisms that drive ischemia/reperfusion injury are not well understood; currently, few methods can predict the state of the cardiac muscle cell and its metabolic conditions during ischemia. Here, we explored the energetic sustainability of cardiomyocytes, using a model for cellular metabolism to predict the levels of ATP following hypoxia. We modeled glycolytic metabolism with a system of coupled ordinary differential equations describing the individual metabolic reactions within the cardiomyocyte over time. Reduced oxygen levels and ATP consumption rates were simulated to characterize metabolite responses to ischemia. By tracking biochemical species within the cell, our model enables prediction of the cell’s condition up to the moment of reperfusion. The simulations revealed a distinct transition between energetically sustainable and unsustainable ATP concentrations for various energetic demands. Our model illustrates how even low oxygen concentrations allow the cell to perform essential functions. We found that the oxygen level required for a sustainable level of ATP increases roughly linearly with the ATP consumption rate. An extracellular O2 concentration of ~0.007 mM could supply basic energy needs in non-beating cardiomyocytes, suggesting that increased collateral circulation may provide an important source of oxygen to sustain the cardiomyocyte during extended ischemia. Our model provides a time-dependent framework for studying various intervention strategies to change the outcome of reperfusion.
2020-08-25 | BIOMD0000000961 | BioModels
Project description:Disruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on circadian rhythm proteins in the heart indicated a role for Clock or Per2 in cardiac metabolism. In fact, Per2-/- mice have larger infarct sizes with a deficient lactate production during myocardial ischemia. To test the hypothesis that cardiac Per2 represents an important regulator of cardiac metabolism during myocardial ischemia, we performed lactate measurements during reperfusion in Per1-/-, Per2-/- or wildtype mice followed by gene array studies using various ischemia-reperfusion protocols comparing wildtype and Per2-/- mice. Lactate measurements in whole blood confirmed a dominant role of Per2 for lactate production during myocardial ischemia. Surprisingly, high-throughput gene array analysis of eight different conditions on one 24-microarray plate revealed dominantly lipid metabolism as differentially regulated pathway in wildtype mice when compared to Per2-/-. In all treatment groups, the enzyme enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was regulated in wildtype animals only. Studies using nuclear magnet resonance imaging (NMRI) confirmed altered fatty acid populations with higher mono-unsaturated fatty acid levels in hearts from Per2-/- mice. Unexpectedly, studies on gene regulation during reperfusion revealed solely pro inflammatory genes as differentially regulated 'Per2-genes'. Subsequent studies on inflammatory markers showed increasing IL6 or TNFa levels during reperfusion in Per2-/- mice. In summary, these studies reveal a novel role of cardiac Per2 for fatty acid metabolism or inflammation during myocardial ischemia and reperfusion. We pursued studies on Per2 dependent gene expression during myocardial ischemia or reperfusion to understand its impact on cardiac metabolism. We designed different ischemia and reperfusion protocols and performed a high-throughput expression profiling of 24 samples at a time using an industry-standard whole mouse gene array (Affymetrix, Mouse Gene 2.1 ST 24-Array). To understand differential gene regulation during different conditions we performed 1) 30 minutes of ischemia without reperfusion, 2) ischemic preconditioning (IP, 4 x 5 minutes ischemia and reperfusion), as known cardioprotective mechanism, and 3) 30 minutes of ischemia followed by 60 minutes of reperfusion. Based on three arrays per condition the total number of arrays was 24, which we analyzed at the same time on a multi plate array to avoid inter-array variations. Quality analysis using Partek Genomics Suite 6.6 revealed high confidence in the quality of the microarray data and all samples met 'Quality Assurance/Quality Control' (QA/QC) criteria.
2013-08-21 | E-GEOD-45818 | biostudies-arrayexpress
Project description:Ischemia reperfusion injury (IRI) following intervention for myocardial infarction remains an unmet clinical problem. Using an established mouse model, we demonstrated that IRI induces multiple cardiac cell linages to senescence. Senescence is is detrimental to recovery, as treatment with the senolytic navitoclax improves functional recovery.Here we are using SWATH-MS to investigate the molecular mechanisms responsible for the effect of navitoclax treatment.
2020-02-29 | MSV000085040 | MassIVE
Project description:Coronary heart disease is the leading cause of death worldwide. After an acute myocardial infarction, early reperfusion reduces infarct size, which correlates with improved clinical outcomes. Paradoxically, reperfusion although relieving ischemia, accelerates apoptosis in injured cardiomyocytes, which has led to the view that myocardial salvage is futile beyond the first few hours of reperfusion. In murine hearts subjected to 90 min of coronary artery occlusion and then 48 h of reperfusion, we show transient activation of intrinsic prosurvival insulin-like growth factor-1 (IGF-1) signaling. In these hearts, acute IGF-1 receptor inhibition decreases the abundance of prosurvival signaling molecules, and markedly activates caspase-3, a potent effector of apoptosis, in infarct border zone cardiomyocytes. We found that mouse mast cell protease-4 (MMCP-4) degraded IGF-1 in vitro by a novel catalytic activity of chymases. In vivo, this degradation, which is triggered by mast cell infiltration into the peri-infarct region and MMCP-4 extravasation, between 48 and 72 h post-ischemia/reperfusion (I/R), attenuates IGF-1 prosurvival signaling. In MMCP-4-deficient mice, while infarct size is not reduced at 24 h post-I/R, at 72 h post-I/R myocardial IGF-1 levels and signaling are increased, resulting in activation of the survival kinases Akt and ERK, inhibition of caspase-3, and reduced myocardial cell death. As a consequence, I/R-mediated loss of viable myocardium, adverse cardiac remodeling and contractile impairment are markedly reduced. Cardiomyocyte survival with consequent myocardial salvage may thus be possible even days after an ischemic insult, making them a novel therapeutic target for delayed cardioprotective therapy. Group 1 is wild type C57Bl6 uninjured hearts. These mice were not undergone any surgery and used as controls. Group 2 are wild type C57Bl6 72 h post-ischemia reperfusion (IR) injury hearts. These mice for subjected to ischemia reperfusion (IR) involving 90 min of left anterior descending coronary artery occlusion followed by reperfusion for 3 days or 72 h.
2015-09-01 | E-GEOD-61592 | biostudies-arrayexpress
Project description:Aims: Mesenchymal stem cells (MSCs) gradually become attractive candidates for cardiac inflammation modulation, yet understanding of the mechanism remains elusive. Strikingly, recent studies indicated that exosomes secreted by MSCs might be a novel mechanism for the beneficial effect of MSCs transplantation after myocardial infarction. We therefore explored the role of MSC-derived exosomes (MSC-Exo) in the immunomodulation of macrophages after myocardial ischemia-reperfusion and its implications in cardiac injury repair. Methods and Results: Exosomes were isolated from the supernatant of MSCs using a gradient centrifugation method. Administration of MSC-Exo through intramyocardial injection after myocardial ischemia reperfusion reduced infarct size and alleviated inflammation level in heart and serum. Systemic depletion of macrophages with clodronate liposomes abolished the curative effects of MSC-Exo. MSC-Exo modified the polarization of M1 macrophages to M2 macrophages both in vivo and in vitro. miRNA-sequencing of MSC-Exo and bioinformatics analysis implicated miR-182 as a potent candidate mediator of macrophage polarization and TLR4 as a downstream target. Diminishing miR-182 in MSC-Exo partially attenuated its modulation of macrophage polarization. Likewise, knock down of TLR4 also conferred cardioprotective efficacy and reduced inflammation level in a mouse model of myocardial ischemia/reperfusion. Conclusion: Our data indicates that MSC-Exo attenuates myocardial ischemia/reperfusion injury via shuttling miR-182 that modifies the polarization state of macrophages. This study sheds new light on the application of MSC-Exo a potential therapeutic tool for myocardial ischemia/reperfusion injury.
2021-09-01 | GSE120149 | GEO