GEO DataSets

(Submitter supplied) Arrhythmogenic cardiomyopathy (ACM) is characterized by life-threatening ventricular arrhythmias and sudden cardiac death and affects hundreds of thousands of patients worldwide. The deletion of Arginine 14 (p.R14del) in the phospholamban (PLN) gene has been implicated in the pathogenesis of ACM. PLN is a key regulator of sarcoplasmic reticulum (SR) Ca2+ cycling and cardiac contractility. Despite global gene and protein expression studies, the molecular mechanisms of PLN-R14del ACM pathogenesis remain unclear. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL24676

6 Samples

Download data: TAB

(Submitter supplied) We utilized humanized wild-type and R14 deletion (R14del) phospholamban (PLN) knock-in mice to determine the role of the inherited PLN-R14del on malignant right ventricular arrhythmias.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

12 Samples

Download data: TXT

(Submitter supplied) Phospholamban R14del mutazion (PLN-R14del) has been identified in a large family pedigree in which heterozygous carriers exhibited inherited dilated cardiomyopathy (DCM) and death by middle age. To better understand the causal link between the mutations in PLN and DCM pathology, we derived induced pluripotent stem cells from a DCM patient carrying the PLN R14del mutation. We showed that iPSC-derived cardiomyocytes recapitulated the DCM-specific phenotype and demonstrated that either TALEN-mediated genetic correction or combinatorial gene therapy resulted in phenotypic rescue. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

3 Samples

Download data: TXT

(Submitter supplied) Background: The p.(Arg14del) pathogenic variant (R14del) of the phospholamban (PLN) gene is a prevalent cause of cardiomyopathy with heart failure. The exact underlying pathophysiology is unknown, and a suitable therapy is unavailable. We aim to identify molecular perturbations underlying this cardiomyopathy in a clinically relevant PLN-R14del mouse model. Methods: We investigated progression of cardiomyopathy in PLN-R14∆/∆ mice using echocardiography, electrocardiography and histological tissue analysis. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

39 Samples

Download data: TXT

(Submitter supplied) Heart failure (HF) is a major cause of morbidity and mortality worldwide, but therapeutic intervention remains limited despite recent improvements. Aberrant Ca2+ handling is a key feature of HF pathophysiology. Restoring the Ca2+ regulating machinery is an attractive therapeutic strategy supported by genetic and pharmacological proof of concept studies. Here, we studied antisense oligonucleotides (ASOs) as a novel therapeutic modality, interfering with the PLN/SERCA2a interaction by targeting Pln mRNA for downregulation in the heart of murine HF models. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

20 Samples

Download data: TXT

(Submitter supplied) Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. Our laboratories have previously developed 2 mouse models that affect cardiac performance. One transgenic mouse model encodes an FHC-associated mutation in α-tropomyosin (Tm180) that displays severe cardiac hypertrophy with fibrosis and impaired physiological performance. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

24 Samples

Download data: CEL, CHP

(Submitter supplied) These mice have been genetically modified so that the mouse PLN gene has been replace with the human PLN gene. Phopspholamban (PLN), the reversible inhibitor of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), is a key regulator of myocyte Ca2+-cycling with a significant role in heart failure. We previously showed that the single amino acid difference between human and mouse PLN results in increased inhibition of Ca2+-cycling, cardiac remodeling and attenuated stress responses, in transgenic mice expressing the human PLN in the null background (hPLN). more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL2897

12 Samples

Download data: TXT

(Submitter supplied) Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are used to examine in vitro the effect of mutations in the cardiac sodium channel gene SCN5A, associated with cardiac arrhythmias. Postnatally SCN5A undergoes a fetal-to-adult isoform switch, but hiPSC-CMs in conventional 2-dimensional cultures are fetal-like. This impedes evaluation of mutations in the adult isoform. Here, we derived hiPSC-CMs from a patient carrying compound mutations in the adult SCN5A exon 6B and in exon 4 and generated isogenic corrected lines. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

8 Samples

Download data: TXT

(Submitter supplied) Since Tead1 binds to MCAT promoter elements to regulate many muscle-specific genes, we performed a global transcriptome analysis in Tead1-deleted adult mouse hearts to assess Tead1 regulated pathways critical to CM function.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL13912

6 Samples

Download data: TXT