Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA237182 | ENA |
REPOSITORIES: ENA
Similar Datasets
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: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.
2014-05-26 | GSE54612 | GEO
Project description:Adverse cardiac remodeling after myocardial infarction (MI) causes structural and functional changes in the heart leading to heart failure. The initial pro-inflammatory response followed by an anti-inflammatory or reparative response post-MI is essential for minimizing the myocardial damage, healing, and scar formation. Bone marrow-derived macrophages (BMDMs) are recruited to the injured myocardium and essential for cardiac repair as they can adopt both pro-inflammatory (M1) or anti-inflammatory/reparative (M2) phenotypes to modulate inflammatory and reparative response, respectively. YAP and TAZ are the key mediators of the Hippo signaling pathway and essential for cardiac regeneration and repair. However, their role in macrophage polarization and post-MI inflammation, remodeling, and healing are not well established. Here, we demonstrate that expression of YAP and TAZ is increased in macrophages undergoing M1 or M2 polarization. Genetic deletion of YAP/TAZ leads to impaired M1 polarization and enhanced M2 polarization. Consistently, YAP activation/overexpression enhanced M1 and impaired M2 polarization. We show that YAP/TAZ promote M1 polarization by increasing IL6 expression, and impede M2 polarization by decreasing Arg1 expression through interaction with the HDAC3-NCoR1 repressor complex. These changes in macrophages polarization due to YAP/TAZ deletion results in reduced fibrosis, and hypertrophy and increased angiogenesis, leading to improved cardiac function after MI. Also, YAP activation augmented MI-induced cardiac fibrosis and remodeling. In summary, we identify YAP/TAZ as important regulators of macrophage-mediated pro- and anti-inflammatory responses post-MI.
2020-10-02 | GSE158889 | GEO
Project description:Sexual dimorphisms are well recognized in various cardiac diseases, including myocardial infarction (MI). MI develops later in women, but once established, it contributes more persistent symptoms and higher mortality than in men. Similar observations have been reported in murine model of MI. Although mRNA-level sexual dimorphism of MI have been reported, whether miRNA transcriptome also confers such dimorphism remains unknown. Comprehensive understanding of the mRNA- and miRNA-level genetic programs underlying the heart sexual dimorphisms will expectedly improve clinical outcome by facilitating the development of gender specific treatment strategies. Here, by conducting miRNA microarray analysis of murine MI model samples, we set out to characterize the heart sexual dimorphisms at the level of miRNA transcriptome The left anterior descending (LAD) coronary artery of mice aged 10 weeks was surgically ligated to create extensive MI. The ventricular septum of the areas at risk of ischemia was sampled on post-operative day 28. Total RNA was extracted using Sepasol solution (Sepasol-RNA I super G, nakalai tesque, Japan), and microarray analysis was performed using Affymetrix GeneChip® miRNA 3.0 Arrays
2016-01-07 | E-GEOD-76592 | biostudies-arrayexpress
Project description:Sexual dimorphisms are well recognized in various cardiac diseases, including myocardial infarction (MI). MI develops later in women, but once established, it contributes more persistent symptoms and higher mortality than in men. Similar observations have been reported in murine model of MI. Although mRNA-level sexual dimorphism of MI have been reported, whether miRNA transcriptome also confers such dimorphism remains unknown. Comprehensive understanding of the mRNA- and miRNA-level genetic programs underlying the heart sexual dimorphisms will expectedly improve clinical outcome by facilitating the development of gender specific treatment strategies. Here, by conducting miRNA microarray analysis of murine MI model samples, we set out to characterize the heart sexual dimorphisms at the level of miRNA transcriptome
2016-01-07 | GSE76592 | GEO
Project description:Cardiac hypertrophy can lead to heart failure, and is induced either by physiological stimuli eg postnatal development, chronic exrcise training or pathological stimuli eg pressure or volume overload. This data set looks at microRNA profiles in mouse models to examine whether phosphoinositide 3-kinase (p110 alpha isoform) activity is critical for the maintenance of cardiac function and long term survival in a seeting of heart failure (myocardial infarction). The significance and expected outcome are to recognise genes involved in models of heart failure and attempt to examine underlying regulator pathways involved in possible cardica maintenance in the PI3K mouse model. The matching mRNA gene expression profile (GSE7487) is examined to look for mRNA and microRNA interactions. miRNA expression correlates directly with cardiac function. PI3K regulon ameliorates cardiac stress. Keywords: microRNA profiling, regulatory pathway discovery, genotype comparison Ntg (non-transgenics), dnPI3K (cardiac-specific transgenic model with reduced PI3K activity) and caPI3K (transgenic mice with increased PI3K activity) mice at 3-4 months of age were used. Mice were then subjected to myocardial infarction (occlusion of the left anterior descending aorta) and sham (open heart surgery) for 8 weeks. Left ventricles were harvested. The resulting 6 experimental models were profiled accordingly. The assignment of the mouse models is as follows: caPI3K Sham, Ntg Sham, dnPI3K Sham, caPI3K MI (myocardial infarction), Ntg MI and dnPI3K MI with n = 4 in each group.
2010-05-06 | E-GEOD-14267 | biostudies-arrayexpress
Project description:Coronary heart disease is a main cause of death in the developed world and treatment success remains modest with high mortality rates within one year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases including heart disease. Here, we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression in a mouse model of MI. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared to controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work highlights telomerase activation as a novel therapeutic strategy to prevent heart failure after MI.
2014-12-15 | GSE62973 | GEO
Project description:Biological Relevance and Intent of the Experiment: The objective of this study is to elucidate the role of Cdk1 in cardiac function, specifically its contribution to cardiomyocyte (CM) proliferation and response to injury. Using a heart-specific Cdk1 knockout mouse model, we investigate the molecular and cellular impact of Cdk1 deficiency in the context of myocardial infarction (MI). Cdk1 is known for its regulatory functions in cell cycle progression, and its absence may significantly affect cardiac repair mechanisms post-MI. This research aims to explore whether the lack of Cdk1 impairs CM regeneration or promotes maladaptive remodeling, leading to compromised cardiac function. Overview of the Experimental Workflow: We performed RNA-sequencing (RNA-seq) on heart tissue collected from both wild-type (WT) and cardiac-specific Cdk1 knockout mice subjected to experimental MI. Heart samples were collected 4 days to capture dynamic transcriptional changes associated with Cdk1 loss. Comparative transcriptomic analysis between WT and knockout samples will reveal differentially expressed genes and signaling pathways involved in cardiomyocyte proliferation, apoptosis, and fibrosis. These insights may uncover key pathways driving heart regeneration or degeneration in the absence of Cdk1.
2024-10-31 | E-MTAB-14505 | biostudies-arrayexpress
Project description:Coronary heart disease is a main cause of death in the developed world and treatment success remains modest with high mortality rates within one year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases including heart disease. Here, we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression in a mouse model of MI. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared to controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work highlights telomerase activation as a novel therapeutic strategy to prevent heart failure after MI. Mice of one year of age were left untreated (control) or injected with 5*10^11 adeno associated viruses particles of serotype 9 (AAV9) that carry either en empty expression cassette or express telomerase under control of the CMV promoter. Virus injected mice then underwent myocardial infarction induced through permenant left anterior descending artery (LAD) ligation. Mice that survived for six weeks after LAD ligation were sacrificed and 4 hearts per group (AAV9-empty or AAV9-Tert) and 3 control hearts (no virus treatment, no ligation) were subjected to total RNA isolation for micro array analysis.
2014-12-15 | E-GEOD-62973 | biostudies-arrayexpress
Project description:Phospholamban Antisense Oligonucleotides Improve Cardiac Function in Murine Cardiomyopathy
| PRJNA634911 | ENA