Expression data from mouse heart treated with 2-methyl-2-thiazoline
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE171821 | GEO | 2021/04/10
REPOSITORIES: GEO
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Project description:Myocardial infarct size (IS) and now reflow are major determinants of prognosis and currently there are no effective treatments. We investigated the effects of empagliflozin on cardiac cell populations affected by myocardial ischemia reperfusion injury (IRI), and its cardioprotective potential in terms of IS and no-reflow.
2024-09-13 | GSE255933 | GEO
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: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)
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Project description:Ischemic heart failure after acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. We recently reported that activation of a trans-valvular axial-flow pump in the LV and delaying myocardial reperfusion, known as Primary Unloading, limits infarct size by reducing LV wall stress and increasing expression of the cardioprotective cytokine, stromal derived factor 1 alpha (SDF1a). The mechanisms underlying the cardioprotective benefit and sustained effect of Primary Unloading remain poorly understood. We now tested the importance of delayed reperfusion, the functional significance of SDF1a, and the late-term impact on myocardial function and scar size associated with Primary Unloading. Adult male swine were subjected to Primary Reperfusion or Primary Unloading after 90 minutes of left anterior descending artery occlusion. Compared to Primary Reperfusion, 30 minutes of Primary Unloading was necessary and sufficient prior to reperfusion to limit infarct size. Primary Unloading was associated with a global shift in gene expression within the infarct zone favoring cardioprotection. Compared to Primary Reperfusion, Primary Unloading for 30 minutes preserved SDF1a protein levels without changing SDF1a mRNA levels within the infarct zone and further promoted a shift towards anti-apoptotic signaling within the infarct zone. Primary Unloading reduced activity levels of proteases known to degrade SDF1a and blocking the SDF1a receptor, CXCR4, attenuated the cardioprotective effect of Primary Unloading. Primary Unloading further reduced LV scar size, improved cardiac function, limited expression of markers associated with heart failure and maladaptive remodeling within the non-infarct zone 28 days after acute myocardial infarction. In conclusion, we introduce that Primary Unloading for 30 minutes before, not after reperfusion limits infarct size, increases SDF1a levels within the infarct zone, and results in a durable reduction in LV scar size, improved cardiac function, and limits markers of heart failure and maladaptive remodeling 28 days after AMI.
2018-10-25 | GSE108644 | GEO
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: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.
2015-09-01 | GSE61592 | GEO
Project description:We reported previously that chronic treatment with the Cyclooxygenase-2 inhibitor, rofecoxib, increased acute mortality in rats exposed to ischemia/reperfusion injury (I/R). This manifestation of hidden cardiotoxicity was attributed to the proarrhythmic effect of the drug on the ischemic heart. However, rofecoxib also had beneficial effects on ischemic injury, manifesting as decreased infarct size. In the present study, we aimed to identify molecular changes caused by chronic rofecoxib treatment in the heart. Rats were treated with 5.12 mg/kg rofecoxib or its vehicle for four weeks. Messenger RNA (mRNA), microRNA (miRNA) deep sequencing data, and proteomic datasets of left ventricular tissue samples were used for an unbiased differential expression analysis followed by in silico molecular network analysis and experimental target validation. Using mass spectrometry and filtering criteria, 26 proteins were identified that exhibited pronounced changes in protein expression or phosphorylation due to chronic rofecoxib treatment. The transcriptomic analysis showed mild alterations in the heart´s mRNA- and miRNA expression. The posttranscriptional regulation of mRNAs by miRNAs did not result in differential protein expression. This is the first demonstration that chronic rofecoxib treatment affects posttranslational modification and expression of several proteins in the heart. These are potential off-target effects that could account for the hidden cardiotoxic and/or cardioprotective effects of rofecoxib.
2024-10-30 | E-MTAB-13913 | biostudies-arrayexpress
Project description:We reported previously that chronic treatment with the Cyclooxygenase-2 inhibitor, rofecoxib, increased acute mortality in rats exposed to ischemia/reperfusion injury (I/R). This manifestation of hidden cardiotoxicity was attributed to the proarrhythmic effect of the drug on the ischemic heart. However, rofecoxib also had beneficial effects on ischemic injury, manifesting as decreased infarct size. In the present study, we aimed to identify molecular changes caused by chronic rofecoxib treatment in the heart. Rats were treated with 5.12 mg/kg rofecoxib or its vehicle for four weeks. Messenger RNA (mRNA), microRNA (miRNA) deep sequencing data, and proteomic datasets of left ventricular tissue samples were used for an unbiased differential expression analysis followed by in silico molecular network analysis and experimental target validation. Using mass spectrometry and filtering criteria, 26 proteins were identified that exhibited pronounced changes in protein expression or phosphorylation due to chronic rofecoxib treatment. The transcriptomic analysis showed mild alterations in the heart´s mRNA- and miRNA expression. The posttranscriptional regulation of mRNAs by miRNAs did not result in differential protein expression. This is the first demonstration that chronic rofecoxib treatment affects posttranslational modification and expression of several proteins in the heart. These are potential off-target effects that could account for the hidden cardiotoxic and/or cardioprotective effects of rofecoxib.
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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
Project description:Right ventricular samples were serially acquired during surgical repair of ventricular septal defect. Expression profiling revealed three patterns of gene expression: (1) increased expression above control levels within one hour of cardioplegic arrest, with further amplification during early reperfusion; (2) increased expression limited to the reperfusion phase; and (3) reduced expression during reperfusion. Experiment Overall Design: 4 replicates each: Experiment Overall Design: Stage2, End-ischemia Experiment Overall Design: Stage1, Immediately post-cardioplegic arrest Experiment Overall Design: Stage3, After 5 min. Reperfusion
2008-06-14 | E-GEOD-6381 | biostudies-arrayexpress