ArticleESC heart failure2025
Trametinib alters contractility of paediatric Noonan syndrome-associated hypertrophic myocardial tissue slices.
Article in ESC heart failure, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Berberine Attenuates Hypertrophic Phenotype in RAF1-Mutant Induced Pluripotent Stem Cell-Derived Cardiomyocytes through Suppression of ERK5-Cyclin D1 Signaling.Cardiovascular drugs and therapy · 2026Article
- From Genotype to Cardiac Phenotype: Cardiovascular Involvement in Syndromic and Metabolic Disorders.International journal of molecular sciences · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Heart Failure in the Modern Era: A Narrative Overview of Recent Research from 2022-2025.Journal of cardiovascular development and disease · 2025Review
- Living myocardial slices retain patient-specific features: Insights into etiology and therapeutic history.JHLT open · 2025Article
- Living myocardial slices: walking the path towards standardization.Cardiovascular research · 2025Review
- Trametinib alters contractility of paediatric Noonan syndrome-associated hypertrophic myocardial tissue slices.ESC heart failure · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
aimsNo curative treatment is available for RASopathy-associated childhood-onset hypertrophic cardiomyopathy (RAS-CM). Preclinical data and individual reports suggest a beneficial effect of small molecules targeting the RAS-mitogen-activated protein (MAP) kinase (MAPK) pathway in severely affected RAS-CM patients. The aim of this study was to evaluate the biophysical effects of trametinib, rapamycin and dasatinib on cultivated myocardial tissue slices of a paediatric RAS-CM patient using biomimetic cultivation chambers (BMCCs) and to correlate the findings with clinical data.
methodsContracting right ventricular (RV) tissue slices were prepared from resected myocardium, cultivated in BMCCs and treated with distinct molecules directly and indirectly targeting the RAS-MAPK pathway (trametinib, rapamycin and dasatinib) or dimethyl sulfoxide (DMSO). Tissue biophysical properties were assessed using electrical stimulation protocols. Contractile function, force-frequency relationship and post-pause potentiation were compared before and after treatment. These parameters correlated to L-type Ca
resultsIn vivo, off-label treatment with MAPK kinase (MEK) inhibitor trametinib of a child with severe RAS-CM resulted in a modest reduction of RV outflow tract (RVOT) obstruction (RVOT 151 to 122 mmHg after 11 weeks) and improved diastolic function (E/A 0.68 to 1.09 after 11 weeks) and myocardial strain [RV global radial strain (RV-GRS) 25.94 to 42.76; RV global circumferential strain (RV-GCS) -15.26 to -18.61; and RV global longitudinal strain (RV-GLS) -10.31 to -16.78 at 11 weeks], as determined by echocardiography and cardiac magnetic resonance tomography. In cultivated RV myocardial tissue slices, contraction force decreased after addition of trametinib and rapamycin but not after addition of DMSO and dasatinib. Improvement of Ca
conclusionsEx vivo analysis of cultivated and electrically stimulated RV myocardial tissue slices of a patient with RAS-CM showed decreased contractility and improved sarcoplasmic reticulum function after addition of trametinib and in part after addition of rapamycin, but not after addition of dasatinib.
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