Omics · study · 2026
Studying the effect of sarcomeric MYH7R663H and non-sarcomeric BRAFT599R hypertrophic cardimyopathy mutations in human induced pluripotent stemm cell-derived cardiomyocytes
Listed in NCBI GEO
Activating mutations in the RAS-MAPK pathway account for ~20% of cases of paediatric hypertrophic cardiomyopathy (HCM) and are associated with poor outcomes.
Description
Mavacamten is approved for obstructive HCM; however, patients with RAS-associated HCM have not been included in the clinical trials so far. We aimed to characterize the functional and energetic disturbances in an in vitro RAS-HCM model and evaluate the therapeutic effects of mavacamten.
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying a CRISPR-induced BRAF (p.Thr599Arg) mutation and their isogenic control were studied. Cell size, contractility, and transcriptomics were assessed, while energetics were determined using MitoStress assays, live ATP imaging, and NAD(P)H/FAD autofluorescence. BRAF-mutant hiPSC-CMs showed hypertrophy, hypercontractility, increased mitochondrial cofactor pools, and enhanced maximal respiratory capacity.
Read the rest (2 more)
Despite this, they developed ATP deficiency in response to rapid pacing, suggesting mitochondrial inefficiencies or an overwhelming ATP demand. Mavacamten normalized mitochondrial respiration and excessive ATP consumption, partially restoring energetic balance and highlighting hypercontractility as a major burden in RAS-HCM. BRAF-mutant cardiomyocytes recapitulate the characteristics of HCM in vitro.
Mavacamten mitigates dysfunctions and restores energetic balance under stress conditions, indicating it holds potential as a therapeutic option for RASopathy-associated HCM.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE332nnn/GSE332763 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE332763 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1469061 ncbi.nlm.nih.gov/bioproject/PRJNA1469061 ↗
project · from NCBI GEO
- PubMed 42332248 pubmed.ncbi.nlm.nih.gov/42332248 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cardiomyopathy 75% · Hypertrophic cardiomyopathy 75% · Imaging 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE332763 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cardiomyopathy | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:hypertrophic-cardiomyopathy | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:imaging | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |