Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA279480 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of heart of Hypoxia-inducible 2 alpha-deficient mice, specific in cardiomyocytes (Hif2aloxP/loxP Myosin Cre+) subjected to myocardial ishcemia reperfusion. Hif2a belongs to the family of transcription factors, that regulate a transcriptional response to tissue hypoxia.
2016-12-31 | GSE67308 | 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.
2024-09-02 | BIOMD0000000961 | BioModels
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: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:Early reperfusion of ischemic cardiac tissue remains the most effective intervention for improving clinical outcome following myocardial infarction. However, abrupt increases in intracellular Ca2+ during myocardial reperfusion cause cardiomyocyte death and consequent loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Cardiac IR is accompanied by dynamic changes in expression of microRNAs (miRNAs), which inhibit specific mRNA targets. miR-214 is up-regulated during ischemic injury and heart failure in mice and humans, but its potential role in these processes is unknown. We show that genetic deletion of miR-214 in mice causes loss of cardiac contractility, increased apoptosis, and excessive fibrosis in response to IR injury. The microarray contains 6 samples, each containing cDNA pooled from 3 mice per group. There are no replicates. The array was designed to make 3 different pairwise comparisons between the following: P14 WT and miR-214 KO hearts; adult WT and miR-214 KO skeletal muscle; adult WT and miR-214 KO hearts
2012-01-31 | E-GEOD-35421 | biostudies-arrayexpress
Project description:Early reperfusion of ischemic cardiac tissue remains the most effective intervention for improving clinical outcome following myocardial infarction. However, abrupt increases in intracellular Ca2+ during myocardial reperfusion cause cardiomyocyte death and consequent loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Cardiac IR is accompanied by dynamic changes in expression of microRNAs (miRNAs), which inhibit specific mRNA targets. miR-214 is up-regulated during ischemic injury and heart failure in mice and humans, but its potential role in these processes is unknown. We show that genetic deletion of miR-214 in mice causes loss of cardiac contractility, increased apoptosis, and excessive fibrosis in response to IR injury.
2012-01-31 | GSE35421 | 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: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.
2013-08-21 | GSE45818 | GEO