Transcriptome changes in cardiomyocytes isolated from a rat model of progressive heart failure
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ABSTRACT:
PROVIDER: PRJNA892890 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21999400_1.fastq.gz | Fastqsanger.gz | |||
| SRR21999400_2.fastq.gz | Fastqsanger.gz | |||
| SRR21999401_1.fastq.gz | Fastqsanger.gz | |||
| SRR21999401_2.fastq.gz | Fastqsanger.gz | |||
| SRR21999402_1.fastq.gz | Fastqsanger.gz |
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Project description:Heart failure is among the leading causes of death globally. Ventricular failure progresses through a hypertrophic compensatory phase followed by failure of the ventricle function through rapid decompensation. In order to unravel right heart specific mechanisms of disease, rat animal models were established that (i) reflect the slowly progressive mode of compensation / decompensation and (ii) allow comparative analyses of left versus right heart failure in the same experimental set up. Non-restrictive clips around the pulmonary artery (pulmonary artery banding, PAB) or the aorta (aortic banding, AOB) were surgically implanted into weanling rats. Upon animal growth the clips become increasingly constrictive, leading to a compensatory, hypertrophic state at around 6 weeks and heart failure at 21 (PAB) or 24 weeks (AOB). Disease progression was monitored functionally and by sonography. Differential gene expression analysis was performed for all three treatment groups (sham, AOB, PAB), at both time points (compensation, decompensation) and for both ventricles.
2024-04-15 | GSE216263 | GEO
Project description:Heart failure is among the leading causes of death globally. Ventricular failure progresses through a hypertrophic compensatory phase followed by failure of the ventricle function through rapid decompensation. In order to unravel right heart specific mechanisms of disease, rat animal models were established that (i) reflect the slowly progressive mode of compensation / decompensation and (ii) allow comparative analyses of left versus right heart failure in the same experimental set up. Differential gene expression analysis was performed for all three treatment groups (sham, AOB, PAB), at both time points (compensation, decompensation) and for both ventricles as well as the septum
2024-04-15 | GSE216264 | GEO
Project description:Transcriptome changes in a rat model of progressive heart failure
| PRJNA892889 | ENA
Project description:Heart failure is the final stage of various cardiovascular diseases, which seriously threatens human health. Increasing mediators have been found to be involved in the pathogenesis of heart failure, including RNA binding protein RBFox2. It participates in regulation of cardiac function in multiple aspects and plays a critical role in the process of heart failure. However, how RBFox2 itself is regulated remains unclear. Here, we dissected transcriptomic signatures including mRNAs as well as miRNAs in the mouse model of heart failure after TAC surgery. Global and association analyses revealed that large-scale upregulation of miRNAs occurred at heart failure, which was not only responsible for degradation of numerous mRNA transcripts, but also suppressed the translation of key proteins such as RBfox2. With the aid of Ago2 CLIP-seq data, luciferase assays verified that RBfox2 was targeted by multiple miRNAs including let-7, mir-16 and mir-208b, which were critical for cardiac function and upregulated in heart failure stage. Overexpression of these miRNAs suppressed rbfox2 protein and its downstream effects in cardiomyocytes, evidenced by suppressed alternative splicing of Enah gene and impaired E-C coupling via repression of Jph2 protein. Inhibition of let-7, the most abundant of these miRNAs in the heart, could rescue Rbfox2 protein as well as its downstream effects in dysfunctional cardiomyocytes induced by ISO treatment. These findings not only revealed the mechanism leading to RBFox2 depression in heart failure, but also provided an approach to rescue RBFox2 by miRNAs inhibition for the treatment of heart failure.
2023-01-25 | GSE215301 | GEO
Project description:Heart failure is the final stage of various cardiovascular diseases, which seriously threatens human health. Increasing mediators have been found to be involved in the pathogenesis of heart failure, including RNA binding protein RBFox2. It participates in regulation of cardiac function in multiple aspects and plays a critical role in the process of heart failure. However, how RBFox2 itself is regulated remains unclear. Here, we dissected transcriptomic signatures including mRNAs as well as miRNAs in the mouse model of heart failure after TAC surgery. Global and association analyses revealed that large-scale upregulation of miRNAs occurred at heart failure, which was not only responsible for degradation of numerous mRNA transcripts, but also suppressed the translation of key proteins such as RBfox2. With the aid of Ago2 CLIP-seq data, luciferase assays verified that RBfox2 was targeted by multiple miRNAs including let-7, mir-16 and mir-208b, which were critical for cardiac function and upregulated in heart failure stage. Overexpression of these miRNAs suppressed rbfox2 protein and its downstream effects in cardiomyocytes, evidenced by suppressed alternative splicing of Enah gene and impaired E-C coupling via repression of Jph2 protein. Inhibition of let-7, the most abundant of these miRNAs in the heart, could rescue Rbfox2 protein as well as its downstream effects in dysfunctional cardiomyocytes induced by ISO treatment. These findings not only revealed the mechanism leading to RBFox2 depression in heart failure, but also provided an approach to rescue RBFox2 by miRNAs inhibition for the treatment of heart failure.
2023-01-25 | GSE215302 | GEO
Project description:Despite some success of pharmacotherapies targeting primarily neurohormonal dysregulation, heart failure is a growing global pandemic with increasing burden. Treatments that improve the disease by reversing heart failure at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators of gene expression, acting through complex biological networks, and playing thereby essential roles in disease progression. Adverse structural remodelling of the left ventricle due to myocardial infarction (MI) is a common pathological feature leading to heart failure. We previously demonstrated increased cardiomyocyte expression of the miR-212/132 family during pathological cardiac conditions. Transgenic mice overexpressing the miR-212/132 cluster (miR-212/132-TG) develop pathological cardiac remodelling and die prematurely from progressive HF. Using both knockout and antisense strategies, we have shown miR-132 to be both necessary and sufficient to drive the pathological growth of cardiomyocytes in a murine model of left ventricular pressure overload. Based on the findings, we proposed that miR-132 may serve as a therapeutic target in heart failure therapy. Here we provide novel mechanistic insight and translational evidence for the therapeutic efficacy in small and large animal models (n=135) of heart failure. We demonstrate strong PK/PD relationship, dose-dependent efficacy and high clinical potential of a novel optimized synthetic locked nucleic acid phosphorothioate backbone antisense oligonucleotide inhibitor of miR-132 (antimiR-132) as a next-generation heart failure therapeutic.
2020-01-09 | PXD015337 | Pride
Project description:Suppression of RBFox2 by Multiple MiRNAs Contributed to Progressive Heart Failure
| PRJNA889732 | ENA
Project description:Aim - Pathological cardiac remodeling is characterized by cardiomyocyte hypertrophy and fibroblast activation, which can ultimately lead to heart failure (HF). Genome-wide expression analysis on heart tissue has been instrumental for the identification of molecular mechanisms at play. However, these data were based on signals derived from all cardiac cell types. Here we aimed for a more detailed view on molecular changes driving cardiomyocyte hypertrophy and failure to aid in the development of therapies to reverse maladaptive remodeling. Methods and results - Utilizing cardiomyocyte-specific reporter mice exposed to pressure overload by transverse aortic banding (TAB), we obtained gene expression profiles of hypertrophic (one-week TAB) and failing (eight-weeks TAB) cardiomyocytes. We identified subsets of genes differentially regulated and specific for either stage. Among these, we found upregulation of known marker genes for HF, such as Nppb and Myh7. Additionally, we identified a set of genes specifically upregulated in failing cardiomyocytes and that so far have not been studied in HF, including the platelet isoform of phosphofructokinase (PFKP). Human cardiomyocytes subjected to 7-day NE/AngII treatment recapitulated the upregulation of the failure-induced genes indicating conservation. RNA-seq on failing and healthy human hearts confirmed increased expression for several failure-induced genes and allowed for expressional correlation to NPPB/MYH7. Finally, suppression of Pfkp in PE-treated primary cardiomyocytes reduced stress-induced gene expression and hypertrophy, suggesting a role in cardiomyocyte failure. Conclusion - Using cardiomyocyte-specific transcriptomic analysis we identified novel failure-induced genes relevant for human HF, and show that PFKP is a conserved failure-induced gene that can modulate cardiomyocyte stress response.
2020-09-15 | GSE138299 | GEO
Project description:To investigate molecular profiles of progressive heart failure, we studied mice that lack expression of the muscle LIM protein (MLPKO). These mice showed dramatic HF progression between three and six weeks of age. We then performed gene expression profile analysis using data obtained from RNA-seq of mid wall left ventricular heart tissue from MLPKO mice and wild-type (WT) controls at three, six, and ten weeks of age (n=3 per group).
2023-06-29 | GSE225008 | GEO
Project description:Proteomic analysis of the changes in kidney upon chronic heart failure in a rat model. Heart failure develops due to surgically created aorto-venoufistula.
2018-09-24 | PXD009296 | Pride