Plasma microRNA array analysis following cardiac ischemia-reperfusion (I/R) injury
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE74951 | GEO | 2015/11/13
SECONDARY ACCESSION(S): PRJNA301993
REPOSITORIES: GEO
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Project description:This study was a part of a larger study assessing the response of young pigs to cardiac ischemia/reperfusion (IR) injury. A mild cardiac injury approach (IR) was used in post-weaned pigs (1-month), to assess regenerative repair in young large mammals after transient ischemic injury. Female and male postnatal day (P)30 pigs were subjected to cardiac ischemia (1-hour) by occlusion of the left anterior descending artery followed by reperfusion (IR), or to sham operation. In pigs subjected to IR, myocardial damage occurred, indicated by increased circulating cardiac troponin I 2-hours post-ischemia. In addition, cardiac ejection fraction (EF) was significantly decreased 2-hours post-ischemia and reduced EF was maintained to the 4-week study end-point. Histology demonstrated evidence of CM cell cycling at 2-months of age in multinucleated CMs in both sham-operated and IR pigs. Following IR, regional scar formation and inflammation in the epicardial region proximal to injury were observed 4-weeks post-IR. Sex differences in cardiac function and collagen deposition were found, highlighting the importance of representing both sexes in cardiac injury studies. Together, our results describe an effective novel cardiac injury model in 1-month old swine, at a time when CM are still cycling. However, pigs subjected to IR show a prolonged decrease in cardiac function, and the formation of a small, regional scar with increased inflammation. Together, these data demonstrate that 1-month old pigs do not regenerate myocardium, but form a scar, after transient IR injury.
2020-04-27 | GSE137293 | GEO
Project description:In this study, total 68 immunolog-related miRNAs were detected
2015-11-13 | GSE74952 | GEO
Project description:Primary cardiac myocytes isolated from neonatal Wistar rats were cultured and simulated ischemia/reperfusion injury were conducted on them in the presence or absence of decorin. Decorin is a small leucin-rich proteoglycan, which has a cardiocytoprotective effect. The underlaying mechanism of this cardiocytoprotective phenomenon is unknown, therefore our aim was to investigate the changes in the mRNA expression between the decorin (3nM) treated and vehicle-treated control cells.
2020-12-31 | E-MTAB-9325 | biostudies-arrayexpress
Project description:This RNA-sequencing was performed to determine the differentially expressed mRNA after inhibition of Hmbox1 in cardiac ischemia/reperfusion injury
2024-05-17 | GSE241079 | GEO
Project description:Calpain 1 and 2 (CPN1/2) are calcium-dependent cysteine proteases that exist in cytosol and mitochondria. Pharmacologic inhibition of CPN1/2 decreases cardiac injury during ischemia (ISC) – reperfusion (REP) by improving mitochondrial function. However, the protein targets of CPN1/2 activation during ISC-REP are unclear. CPN1/2 include a large subunit and a small regulatory subunit 1 (CPNS1). Genetic deletion of the CPNS1 eliminates the activities of both CPN1 and CPN2. Conditional, cardiomyocyte specific CPNS1 knockout (KO) mice were used in the present study to clarify the role of CPN1/2 activation in mitochondrial damage during ISC-REP with an emphasis on identifying the potential protein targets of CPN1/2. Isolated hearts from wild type (WT) or CPNS1 KO mice underwent 25 min in vitro global ISC and 30 min REP. LDH activity in coronary effluent was measured to reflect cardiac injury. Mitochondria were isolated from the hearts. Cardiac injury was decreased in CPNS1 KO mice following ISC-REP compared to WT. ISC-REP decreased the rate of oxidative phosphorylation in WT but not in CPNS1 KO mice when glutamate + malate was used as complex I substrate. KO of CPNS1 led to a smaller decrease in CRC (calcium retention capacity) following REP compared to WT. The H2O2 generation was decreased in KO mitochondria following ISC-REP compared to WT. KO of CPNS1 also resulted in less cytochrome c release from mitochondria. Proteomic analysis of the isolated mitochondria showed that KO of CPNS1 increased the abundance of ribosomal proteins and mitochondrial biogenesis proteins. These results show that activation of CPN1/2 increases cardiac injury during ischemia-reperfusion by damaging mitochondria.
2021-12-21 | PXD022689 | Pride
Project description:BACKGROUND:Silver nanoparticles (AgNP) have garnered much interest due to their antimicrobial properties, becoming one of the most utilized nano-scale materials. However, any potential evocable cardiovascular injury associated with exposure has not been reported to date. We have previously demonstrated expansion of myocardial infarction after intratracheal (IT) instillation of carbon-based nanomaterials. We hypothesized pulmonary exposure to Ag core AgNP induces a measureable increase in circulating cytokines, expansion of cardiac ischemia-reperfusion (I/R) injury and is associated with depressed coronary constrictor and relaxation responses. Secondarily, we addressed the potential contribution of silver ion release on AgNP toxicity. METHODS:Male Sprague-Dawley rats were exposed to 200 ?l of 1 mg/ml of 20 nm citrate-capped Ag core AgNP, 0.01, 0.1, 1 mg/ml Silver Acetate (AgAc), or a citrate vehicle by intratracheal (IT) instillation. One and 7 days following IT instillation the lungs were evaluated for inflammation and the presence of silver; serum was analyzed for concentrations of selected cytokines; cardiac I/R injury and coronary artery reactivity were assessed. RESULTS:AgNP instillation resulted in modest pulmonary inflammation with detection of silver in lung tissue and alveolar macrophages, elevation of serum cytokines: G-CSF, MIP-1?, IL-1?, IL-2, IL-6, IL-13, IL-10, IL-18, IL-17?, TNF?, and RANTES, expansion of I/R injury and depression of the coronary vessel reactivity at 1 day post IT compared to vehicle treated rats. Silver within lung tissue was persistent at 7 days post IT instillation and was associated with an elevation in cytokines: IL-2, IL-13, and TNF? and expansion of I/R injury. AgAc resulted in a concentration dependent infarct expansion and depressed vascular reactivity without marked pulmonary inflammation or serum cytokine response. CONCLUSIONS:Based on these data, IT instillation of AgNP increases circulating levels of several key cytokines, which may contribute to persistent expansion of I/R injury possibly through an impaired vascular responsiveness.
| S-EPMC4780684 | biostudies-literature
Project description:Novel therapeutic targets are required to protect the heart against cell death from acute ischemia-reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible to cell death following ischemia-reperfusion in a model of stroke. Although DJ-1 is present in the heart, its role there is currently unclear. We sought to investigate whether mitochondrial DJ-1 may protect the heart against cell death from acute IRI by preventing mitochondrial dysfunction. Overexpression of DJ-1 in HL-1 cardiac cells conferred the following beneficial effects: reduced cell death following simulated IRI (30.4±4.7% with DJ-1 versus 52.9±4.7% in control; n=5, P<0.05); delayed mitochondrial permeability transition pore (MPTP) opening (a critical mediator of cell death) (260±33 s with DJ-1 versus 121±12 s in control; n=6, P<0.05); and induction of mitochondrial elongation (81.3±2.5% with DJ-1 versus 62.0±2.8% in control; n=6 cells, P<0.05). These beneficial effects of DJ-1 were absent in cells expressing the non-functional DJ-1(L166P) and DJ-1(Cys106A) mutants. Adult mice devoid of DJ-1 (KO) were found to be more susceptible to cell death from in vivo IRI with larger myocardial infarct sizes (50.9±3.5% DJ-1 KO versus 41.1±2.5% in DJ-1 WT; n≥7, P<0.05) and resistant to cardioprotection by ischemic preconditioning. DJ-1 KO hearts showed increased mitochondrial fragmentation on electron microscopy, although there were no differences in calcium-induced MPTP opening, mitochondrial respiratory function or myocardial ATP levels. We demonstrate that loss of DJ-1 protects the heart from acute IRI cell death by preventing mitochondrial dysfunction. We propose that DJ-1 may represent a novel therapeutic target for cardioprotection.
| S-EPMC3944257 | biostudies-literature
Project description:RationaleG protein-coupled receptor kinase 2 (GRK2) is an important molecule upregulated after myocardial injury and during heart failure. Myocyte-specific GRK2 loss before and after myocardial ischemic injury improves cardiac function and remodeling. The cardiac fibroblast plays an important role in the repair and remodeling events after cardiac ischemia; the importance of GRK2 in these events has not been investigated.ObjectiveThe aim of this study is to elucidate the in vivo implications of deleting GRK2 in the cardiac fibroblast after ischemia/reperfusion injury.Methods and resultsWe demonstrate, using Tamoxifen inducible, fibroblast-specific GRK2 knockout mice, that GRK2 loss confers a protective advantage over control mice after myocardial ischemia/reperfusion injury. Fibroblast GRK2 knockout mice presented with decreased infarct size and preserved cardiac function 24 hours post ischemia/reperfusion as demonstrated by increased ejection fraction (59.1±1.8% versus 48.7±1.2% in controls; P<0.01). GRK2 fibroblast knockout mice also had decreased fibrosis and fibrotic gene expression. Importantly, these protective effects correlated with decreased infiltration of neutrophils to the ischemia site and decreased levels of tumor necrosis factor-α expression and secretion in GRK2 fibroblast knockout mice.ConclusionsThese novel data showing the benefits of inhibiting GRK2 in the cardiac fibroblast adds to previously published data showing the advantage of GRK2 ablation and reinforces the therapeutic potential of GRK2 inhibition in the heart after myocardial ischemia.
| S-EPMC5085864 | biostudies-literature
Project description:Aims: Myocardial ischemia–reperfusion (I/R) injury severely facilitates cardiomyocyte death and endangers human health. RNA N6-methyladenosine (m6A) methylation modification plays a critical role in cardiovascular diseases. M6A reader YTHDF2 could identify m6a-modified RNA and promote target RNA degradation. Hence, we hypothesized that YTHDF2 impacts I/R injury by regulating RNA stability, in turn revealing the potential regulatory mechanism. Results: Both the mRNA and protein levels of YTHDF2 were upregulated in I/R mice and hypoxia-reoxygenation (H/R)-induced cardiomyocytes. Silencing endogenous YTHDF2 abrogated cardiac dysfunction and lowered infarct size in I/R mice, and forced expression of YTHDF2 aggravated the above-mentioned adverse pathological process. Consistently, the protective effect of silencing YTHDF2 reappeared in cardiomyocytes induced by H/R and erastin. Furthermore, RNA-seq and RIP revealed that YTHDF2 could recognize the m6A modification sites of ferroptosis-related gene SLC7A11 mRNA to promote its degradation both in vivo and in vitro. Inhibition of SLC7A11 also aggravated cardiac function, infarct size and the release of LDH in I/R mice after silencing YTHDF2. The advantageous effect of si-YTHDF2 in H/R injury was reversed by cotransfection with si-SLC7A11, which substantially exacerbated ferroptosis and the production of ROS. Innovation and Conclusion: All of the obtained data demonstrate that the cardioprotective effects of silencing YTHDF2 are accomplished by enhancing SLC7A11 stability and expression and reducing the level of ferroptosis, furnishing novel potential therapeutic targets for treating ischemic cardiac diseases.
2024-08-20 | GSE236721 | GEO
Project description:Efficient clearance and degradation of apoptotic cardiomyocytes by macrophages (termed efferocytosis) are critical for inflammation resolution and restoration of cardiac function after myocardial ischemia/reperfusion (I/R). Here, we define secreted and transmembrane protein 1a (Sectm1a), a cardiac macrophage-enriched gene, as a modulator of macrophage efferocytosis in I/R hearts. Upon myocardial I/R, Sectm1a-KO mice exhibit impaired macrophage efferocytosis, leading to massive accumulation of apoptotic cardiomyocytes, cardiac inflammation, fibrosis, and consequently, exaggerated cardiac dysfunction. By contrast, therapeutic administration of recombinant SECTM1A protein significantly enhances macrophage efferocytosis and improves cardiac function. Mechanistically, SECTM1A can elicit autocrine effects on the activation of glucocorticoid-induced TNF receptor (GITR) at the surface of macrophages, leading to the upregulation of liver X receptor alpha (LXRα) and its downstream efferocytosis-related genes and lysosomal enzyme genes. Our study suggests that Sectm1a-mediated activation of Gitr/LXRα axis could be a promising approach to enhance macrophage efferocytosis for the treatment of myocardial I/R injury.
2024-01-23 | GSE253579 | GEO