MiR-19 protects heart from myocardium infarction
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE126888 | GEO | 2019/02/26
REPOSITORIES: GEO
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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:In this study, we used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted cardiomyocyte proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after myocardial infarction (MI) preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP in the murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing cardiomyocyte apoptosis. Rather, we found that AAV9:hYAP stimulated adult cardiomyocyte proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated cell cycle gene expression, enhanced TGFβ-signaling, and activated of components of the inflammatory response.Cardiac specific YAP activation after MI mitigated myocardial injury after MI, improved cardiac function and mouse survival. These findings suggest that therapeutic activation of hYAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI. Three groups were involved in this study: sham group, AAV9:Luci+MI group and AAV9-YAP+MI group. Each group contained three biological replicates. The sham group had neither myocardial infarction nor AAV injection. The AAV9:Luci +MI(L for brief) group had myocardial infarction and injected with AAV9:Luic. The AAV9:hYAP+MI(YAP for brief) group had myocardial infarction and injected with AAV9:hYAP. 5 days after MI and AAV injection, the heart apexes were collected and the total RNA were isolated for microarray analysis.
2014-05-26 | E-GEOD-54612 | biostudies-arrayexpress
Project description:Purpose: rHCI hydrogel injection improves cardiac function within 2 days of treatment in a mouse model of myocardial infarction. The goal of this study was to determine the differences in gene expression with rHCI hydrogel injection post-myocardial infarction. Methods: Total RNA was isolated from left ventricle tissue of samples and mRNA stranded libraries were prepared and sequenced in Illumina NovaSeq 6000 with a depth of 50 million reads per sample. Differential expression analysis of aligned reads was done to compared gene expression between PBS vs. rHCI, PBS vs. sham, and rHCI vs. sham comparisons. Results: Differentially expressed genes between sham and PBS as well as rHCI and PBS showed known gene signatures of myocardial infarction. Seven differentially expressed genes were detected with rHCI hydrogel injection compared to PBS. Conclusions: The target gene ERDR1 that is downregulated with rHCI injection led to discovery of changes in cardiomyocyte apoptosis and reduction of oxidative stress adducts with rHCI injection post-myocardial infarction.
2023-08-31 | GSE182205 | GEO
Project description:The regeneration potential of the mammalian heart is limited. We found that treatment of beta-blocker robustly enhanced cardiomyocyte proliferation and promoted cardiac regeneration post myocardial infarction. To investigate the gene expression changes, we performed RNA-seq using the hearts treated with beta-blocker for 7 days.
2022-08-30 | GSE186099 | GEO
Project description:The mortality of patients suffering from acute myocardial infarction (AMI) is linearly related to the infarct size. As regeneration of cardiomyocytes from cardiac progenitor cells is minimal in the mammalian adult heart, we have explored a new therapeutic approach which leverages the capacity of nanomaterials to release chemicals over time to promote myocardial protection and infarct size reduction. Initial screening identified two chemicals, FGF1 and CHIR99021 (a Wnt1 agonist/GSK-3 antagonist) which synergistically enhance cardiomyocyte cell cycle in vitro. Poly-lactic-co-glycolic acid (PLGA) nanoparticles (NP) formulated with CHIR99021 and FGF1 (CHIR+FGF1-NPs) provided an effective slow release system for up to 4 weeks. Intramyocardial injection of CHIR+FGF1-NPs enabled myocardial protection via reducing infarct size by 20-30% in mouse or pig models of postinfarction LV remodeling. This LV structural improvement was accompanied by a significant preservation of cardiac contractile function. Further investigation revealed that CHIR+FGF1-NPs resulted in a significant reduction of cardiomyocyte apoptosis and increase of angiogenesis. Thus, using a combination of chemicals and a NP-based prolonged release system that work synergistically, this study demonstrates a novel therapy for LV infarct size reduction in hearts with acute myocardial infarction.
2019-10-17 | GSE138837 | GEO
Project description:Data set contains samples from isolated cells of murine hearts after myocardial infarction (LAD surgery). We used an endothelial tracing system to mark endothelial cells with EGFP prior to infarct. In brief, Cdh5-ERT2+/-;mT/mG mice, which were used at an age of 10-12 weeks. Cre expression was induced by daily intraperitoneal injections of 2 mg tamoxifen for 1 week in all mice. One week after tamoxifen injection, left anterior descending coronary artery ligation surgery was performed, inducing myocardial infarction. We collected samples at homeostasis, days(d) 1, 3, 7, 14 and 28 after infarction and isolated the non-cardiomyocyte fraction for single cell sequencing. Murine scRNA-seq libraries were prepared using Chromium Single Cell 3′ v3 Reagent Kit (10X Genomics), according to manufacturer’s protocols. Raw reads were mapped against a customized version of mm10 (GRCm38.p4) containing sequences of EGFP and tdTomato.
2020-12-15 | E-MTAB-9816 | biostudies-arrayexpress
Project description:After myocardial infarction (MI), the heart fails to renew, and the cardiac microenvironment is irreversibly disrupted. Inactivation of the Hippo signaling pathway can rebuild the post ischemic microenvironment and improve cardiac function. We investigated spatially resolved cellular relationships of neonatal and adult renewal-competent hearts to gain insight into inefficient mammalian heart renewal. Spatial transcriptomics (ST) and single-cell sequencing of adult control hearts and hearts expressing YAP5SA, an active version of the Hippo signaling pathway effector YAP, which models heart renewal, revealed a conserved, renewal-competent cardiomyocyte (CM) population in control hearts and amplified in YAP5SA hearts. This CM population was also found in the wildtype, renewal competent neonatal heart after myocardial infarction, as well as the adult human heart. Cardiac fibroblasts (CFs), expressing complement C3, colocalized with these CMs. In YAP5SA hearts and neonatal hearts post-MI, macrophages (MPs) expressing complement receptor C3ar1 also colocalized, creating a pro-renewal niche composed of the CM, CF and MP triad. Both C3 and C3ar1 loss-of-function in YAP5SA hearts similarly suppressed heart renewal, indicating that C3-expressing CFs, C3ar1-expressing MPs, and complement system signaling play a direct role in heart renewal
2024-01-11 | GSE217828 | GEO
Project description:Background MicroRNAs are potent regulators of biology and disease. The miR-15 family has been shown to regulate cardiomyocyte proliferation and antimiR-based inhibition induces a cardioprotective effect after myocardial infarction in mice. However, systemic delivery of antimiRs leads to accumulation in kidneys and liver, with relatively poor cardiac exposure. pH-responsive injectable hydrogels serve as a sustained-release drug delivery depot and could potentially be used to improve cardiac efficacy of antimiR therapeutics. Objective Examine whether hydrogel can improve local delivery of antimiR-195 in ischemic hearts to increase cardiac efficacy and limit off-target effects. Methods Study the effect of intramyocardial injections of hydrogel-formulated antimiR-195 under both baseline conditions and after ischemic injury. Results Intracardiac injections of UPy-PEG induced a transient inflammatory response that was no longer present 7 days post-injection. In vitro experiments showed that antimiR-195 was released from the gel, and induced microRNA inhibition leading to downstream cardiomyocyte proliferation. In vivo, intramyocardial delivery of antimiR-195 in UPy-PEG enhanced cardiac target de-repression compared to PBS-dissolved antimiR-195, despite a low cardiac retention. After ischemic injury, this translated into a greater therapeutic effect by increasing both target de-repression and cardiomyocyte proliferation. Conclusions UPy-PEG can be used as a cardiac delivery vehicle of antimiRs and intramyocardial injection of UPy-PEG formulated antimiR-195 is sufficient to improve cardiac efficacy of antimiR-195. Follow up experiments in large animals will enable us to assess the true added value of using UPy-PEG to increase cardiac exposure of antimiR therapies.
2022-11-19 | GSE140660 | GEO
Project description:Background MicroRNAs are potent regulators of biology and disease. The miR-15 family has been shown to regulate cardiomyocyte proliferation and antimiR-based inhibition induces a cardioprotective effect after myocardial infarction in mice. However, systemic delivery of antimiRs leads to accumulation in kidneys and liver, with relatively poor cardiac exposure. pH-responsive injectable hydrogels serve as a sustained-release drug delivery depot and could potentially be used to improve cardiac efficacy of antimiR therapeutics. Objective Examine whether hydrogel can improve local delivery of antimiR-195 in ischemic hearts to increase cardiac efficacy and limit off-target effects. Methods Study the effect of intramyocardial injections of hydrogel-formulated antimiR-195 under both baseline conditions and after ischemic injury. Results Intracardiac injections of UPy-PEG induced a transient inflammatory response that was no longer present 7 days post-injection. In vitro experiments showed that antimiR-195 was released from the gel, and induced microRNA inhibition leading to downstream cardiomyocyte proliferation. In vivo, intramyocardial delivery of antimiR-195 in UPy-PEG enhanced cardiac target de-repression compared to PBS-dissolved antimiR-195, despite a low cardiac retention. After ischemic injury, this translated into a greater therapeutic effect by increasing both target de-repression and cardiomyocyte proliferation. Conclusions UPy-PEG can be used as a cardiac delivery vehicle of antimiRs and intramyocardial injection of UPy-PEG formulated antimiR-195 is sufficient to improve cardiac efficacy of antimiR-195. Follow up experiments in large animals will enable us to assess the true added value of using UPy-PEG to increase cardiac exposure of antimiR therapies.
2022-11-19 | GSE140644 | GEO
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